Cathepsin B is a new drug target for traumatic brain injury therapeutics: Evidence for E64d as a promising lead drug candidate

Frontiers in Neurology

Volumn 6, Issue SEP, 2015, Pages

  Hook, Gregory ^a   Jacobsen, J Steven ^b   Grabstein, Kenneth ^c   Kindy, Mark ^d,e   Hook, Vivian ^f,g  

^a American Life Science Pharmaceuticals Inc   (United States)

^b ASTRAZENECA   (United Kingdom)

^c University of Washington   (United States)

^d MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^e RALPH H JOHNSON VA MEDICAL CENTER   (United States)

^f UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^g UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Cathepsin B; Drug; E64d; Protease; Therapeutics; Traumatic brain injury

Indexed keywords

ALOXISTATIN; ALOXISTATIN ACID; BENZYLOXYCARBONYLASPARTYLGLUTAMYLVALYLASPARTYL FLUOROMETHYL KETONE; BENZYLOXYCARBONYLPHENYLALANYLALANYL FLUOROMETHYL KETONE; CARBOBENOXYPHENYLSERINE(2 BENZYL) 2 [METHYL (4 PHENYLBENZOYL)AMINO]BENZOIC ACID; CATHEPSIN B; CATHEPSIN B INHIBITOR; CYSTATIN; CYSTEINE PROTEINASE; MORPHOLINUREA LEUCINEHOMOPHENYLALANINEVINYLSULFONE PHENYL; N (3 PROPYLCARBAMOYLOXIRANE 2 CARBONYL)ISOLEUCYLPROLINE; N (3 PROPYLCARBAMOYLOXIRANE 2 CARBONYL)ISOLEUCYLPROLINE METHYL ESTER; N METHYLPIPERAZINE PHENYLALANINE HOMOPHENYLALANINE VINYLSULFONE PHENYL; N [N (3 CARBOXYOXIRANE 2 CARBONYL)LEUCYL]AGMATINE; SODIUM 3 [(1 ISOBUTOXY 4 METHYLPENTAN 2 YL)CARBAMOYL]OXIRANE 2 CARBOXYLATE; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; APOPTOSIS; AUTOPHAGOSOME; AUTOPHAGY; AXONAL INJURY; BRAIN ARTERY ANEURYSM; BRAIN EDEMA; BRAIN HEMORRHAGE; BRAIN INFECTION; BRAIN ISCHEMIA; COGNITIVE DEFECT; CYTOPLASM; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG EXCRETION; DRUG HALF LIFE; DRUG SAFETY; DRUG TARGETING; DUCHENNE MUSCULAR DYSTROPHY; ENZYME ACTIVITY; ENZYME LOCALIZATION; ENZYME REGULATION; EPILEPSY; EXTRACELLULAR MATRIX; GENE DELETION; GENETIC TRANSCRIPTION; HUMAN; HUNTINGTON CHOREA; INFLAMMATORY PAIN; LYSOSOME; MAXIMUM PLASMA CONCENTRATION; MEMORY DISORDER; MENINGITIS; MOTOR DYSFUNCTION; MULTIPLE SCLEROSIS; MUTAGENESIS; NERVE CELL NECROSIS; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; PAIN; PH; PROTEIN CLEAVAGE; PROTEIN EXPRESSION; PROTEIN TRANSPORT; REVIEW; RHEUMATOID ARTHRITIS; RNA TRANSLATION; SECRETORY VESICLE; SINGLE DRUG DOSE; TERATOGENICITY; TISSUE DISTRIBUTION; TRAUMATIC BRAIN INJURY;

EID: 84944725337     PISSN: None     EISSN: 16642295     Source Type: Journal    
DOI: 10.3389/fneur.2015.00178     Document Type: Review

References (309)

1. Hyder AA, Wunderlich CA, Puvanachandra P, Gururaj G, Kobusingye OC. The impact of traumatic brain injuries: a global perspective. NeuroRehabilitation (2007) 22:341-53.
2. Faul M, Xu LX, Wald M, Coronado V. Traumatic Brain Injury in the United States: Emergency Department visits, Hospitalizations, and Deaths. Atlanta, GA: Centers for Disease Control and Prevention, National Center for Intjury Prevention and Control (2010).
3. Rutland-Brown W, Langlois JA, Thomas KE, Xi YL. Incidence of traumatic brain injury in the United States, 2003. J Head Trauma Rehabil (2006) 21:544-8. doi:10.1097/00001199-200611000-00009
4. Gessel LM, Fields SK, Collins CL, Dick RW, Comstock RD. Concussions among United States high school and collegiate athletes. J Athl Train (2007) 42:495-503.
5. Warden D. Military TBI during the Iraq and Afghanistan wars. J Head Trauma Rehabil (2006) 21:398-402. doi:10.1097/00001199-200609000-00004
6. Saatman KE, Duhaime AC, Bullock R, Maas AI, Valadka A, Manley GT, et al. Classification of traumatic brain injury for targeted therapies. J Neurotrauma (2008) 25:719-38. doi:10.1089/neu.2008.0586
7. Park E, Bell JD, Baker AJ. Traumatic brain injury: can the consequences be stopped? CMAJ (2008) 178:1163-70. doi:10.1503/cmaj.080282
8. McAllister TW. Neurobiological consequences of traumatic brain injury. Dialogues Clin Neurosci (2011) 13:287-300.
9. Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth (2007) 99:4-9. doi:10.1093/bja/aem131
10. Farkas O, Povlishock JT. Cellular and subcellular change evoked by diffuse traumatic brain injury: a complex web of change extending far beyond focal damage. Prog Brain Res (2007) 161:43-59. doi:10.1016/S0079-6123(06)61004-2
11. Corps KN, Roth TL, Mcgavern DB. Inflammation and neuroprotection in traumatic brain injury. JAMA Neurol (2015) 72:355-62. doi:10.1001/jamaneurol.2014.3558
12. Muellner A, Benz M, Kloss CU, Mautes A, Burggraf D, Hamann GF. Microvascular basal lamina antigen loss after traumatic brain injury in the rat. J Neurotrauma (2003) 20:745-54. doi:10.1089/089771503767869971
13. Coles JP, Fryer TD, Smielewski P, Rice K, Clark JC, Pickard JD, et al. Defining ischemic burden after traumatic brain injury using 15O PET imaging of cerebral physiology. J Cereb Blood Flow Metab (2004) 24:191-201. doi:10.1097/01.WCB.0000100045.07481.DE
14. Miley JT, Rodriguez GJ, Qureshi AI. Traumatic intracranial aneurysm formation following closed head injury. J Vasc Interv Neurol (2008) 1:79-82.
15. Unterberg AW, Stover J, Kress B, Kiening KL. Edema and brain trauma. Neuroscience (2004) 129:1021-9. doi:10.1016/j.neuroscience.2004.06.046
16. Nampiaparampil DE. Prevalence of chronic pain after traumatic brain injury: a systematic review. JAMA (2008) 300:711-9. doi:10.1001/jama.300.6.711
17. Grande DJ, Koranda FC, Guthrie D. Monitoring respirations for outpatient surgery. J Dermatol Surg Oncol (1983) 9:338-9. doi:10.1111/j.1524-4725.1983.tb00811.x
18. Scott BN, Roberts DJ, Robertson HL, Kramer AH, Laupland KB, Ousman SS, et al. Incidence, prevalence, and occurrence rate of infection among adults hospitalized after traumatic brain injury: study protocol for a systematic review and meta-analysis. Syst Rev (2013) 2:68. doi:10.1186/2046-4053-2-68
19. Palmer AM, Marion DW, Botscheller ML, Swedlow PE, Styren SD, Dekosky ST. Traumatic brain injury-induced excitotoxicity assessed in a controlled cortical impact model. J Neurochem (1993) 61:2015-24. doi:10.1111/j.1471-4159.1993.tb07437.x
20. Chen H, Richard M, Sandler DP, Umbach DM, Kamel F. Head injury and amyotrophic lateral sclerosis. Am J Epidemiol (2007) 166:810-6. doi:10.1093/aje/kwm153
21. Gardner RC, Burke JF, Nettiksimmons J, Goldman S, Tanner CM, Yaffe K. Traumatic brain injury in later life increases risk for Parkinson's disease. Ann Neurol (2015) 77(6):987-95. doi:10.1002/ana.24396
22. Fleminger S, Oliver DL, Lovestone S, Rabe-Hesketh S, Giora A. Head injury as a risk factor for Alzheimer's disease: the evidence 10 years on; a partial replication. J Neurol Neurosurg Psychiatry (2003) 74:857-62. doi:10.1136/jnnp.74.7.857
23. Annegers JF, Hauser WA, Coan SP, Rocca WA. A population-based study of seizures after traumatic brain injuries. N Engl J Med (1998) 338:20-4. doi:10.1056/NEJM199801013380104
24. Kang JH, Lin HC. Increased risk of multiple sclerosis after traumatic brain injury: a nationwide population-based study. J Neurotrauma (2012) 29:90-5. doi:10.1089/neu.2011.1936
25. Daneshvar DH, Goldstein LE, Kiernan PT, Stein TD, McKee AC. Post-traumatic neurodegeneration and chronic traumatic encephalopathy. Mol Cell Neurosci (2015) 66(Pt B):81-90. doi:10.1016/j.mcn.2015.03.007
26. Narayan RK, Michel ME, Ansell B, Baethmann A, Biegon A, Bracken MB, et al. Clinical trials in head injury. J Neurotrauma (2002) 19:503-57. doi:10.1089/089771502753754037
27. Beauchamp K, Mutlak H, Smith WR, Shohami E, Stahel PF. Pharmacology of traumatic brain injury: where is the "golden bullet"? Mol Med (2008) 14:731-40. doi:10.2119/2008-00050.Beauchamp
28. Wright DW, Yeatts SD, Silbergleit R, Palesch YY, Hertzberg VS, Frankel M, et al. Very early administration of progesterone for acute traumatic brain injury. N Engl J Med (2014) 371:2457-66. doi:10.1056/NEJMoa1404304
29. Powers BJ, Coeytaux RR, Dolor RJ, Hasselblad V, Patel UD, Yancy WS Jr, et al. Updated report on comparative effectiveness of ACE inhibitors, ARBs, and direct renin inhibitors for patients with essential hypertension: much more data, little new information. J Gen Intern Med (2012) 27:716-29. doi:10.1007/s11606-011-1938-8
30. Cruciani M, Malena M. Combination dolutegravir-abacavir-lamivudine in the management of HIV/AIDS: clinical utility and patient considerations. Patient Prefer Adherence (2015) 9:299-310. doi:10.2147/PPA.S65199
31. Chen D, Frezza M, Schmitt S, Kanwar J, Dou QP. Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Curr Cancer Drug Targets (2011) 11:239-53. doi:10.2174/156800911794519752
32. Vasiljeva O, Reinheckel T, Peters C, Turk D, Turk V, Turk B. Emerging roles of cysteine cathepsins in disease and their potential as drug targets. Curr Pharm Des (2007) 13:387-403. doi:10.2174/138161207779313542
33. Gondi CS, Rao JS. Cathepsin B as a cancer target. Expert Opin Ther Targets (2013) 17:281-91. doi:10.1517/14728222.2013.740461
34. Palermo C, Joyce JA. Cysteine cathepsin proteases as pharmacological targets in cancer. Trends Pharmacol Sci (2008) 29:22-8. doi:10.1016/j.tips.2007.10.011
35. Yan S, Sloane BF. Molecular regulation of human cathepsin B: implication in pathologies. Biol Chem (2003) 384:845-54. doi:10.1515/BC.2003.095
36. Kos J, Mitrovic A, Mirkovic B. The current stage of cathepsin B inhibitors as potential anticancer agents. Future Med Chem (2014) 6:1355-71. doi:10.4155/fmc.14.73
37. Van Acker GJ, Saluja AK, Bhagat L, Singh VP, Song AM, Steer ML. Cathepsin B inhibition prevents trypsinogen activation and reduces pancreatitis severity. Am J Physiol Gastrointest Liver Physiol (2002) 283:G794-800. doi:10.1152/ajpgi.00363.2001
38. Canbay A, Guicciardi ME, Higuchi H, Feldstein A, Bronk SF, Rydzewski R, et al. Cathepsin B inactivation attenuates hepatic injury and fibrosis during cholestasis. J Clin Invest (2003) 112:152-9. doi:10.1172/JCI17740
39. Hashimoto Y, Kakegawa H, Narita Y, Hachiya Y, Hayakawa T, Kos J, et al. Significance of cathepsin B accumulation in synovial fluid of rheumatoid arthritis. Biochem Biophys Res Commun (2001) 283:334-9. doi:10.1006/bbrc.2001.4787
40. Yoshifuji H, Umehara H, Maruyama H, Itoh M, Tanaka M, Kawabata D, et al. Amelioration of experimental arthritis by a calpain-inhibitory compound: regulation of cytokine production by E-64-d in vivo and in vitro. Int Immunol (2005) 17:1327-36. doi:10.1093/intimm/dxh311
41. Chandran K, Sullivan NJ, Felbor U, Whelan SP, Cunningham JM. Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection. Science (2005) 308:1643-5. doi:10.1126/science.1110656
42. Hoegen T, Tremel N, Klein M, Angele B, Wagner H, Kirschning C, et al. The NLRP3 inflammasome contributes to brain injury in pneumococcal meningitis and is activated through ATP-dependent lysosomal cathepsin B release. J Immunol (2011) 187:5440-51. doi:10.4049/jimmunol.1100790
43. McKerrow JH, Rosenthal PJ, Swenerton R, Doyle P. Development of protease inhibitors for protozoan infections. Curr Opin Infect Dis (2008) 21:668-72. doi:10.1097/QCO.0b013e328315cca9
44. Alkhouri N, Carter-Kent C, Feldstein AE. Apoptosis in nonalcoholic fatty liver disease: diagnostic and therapeutic implications. Expert Rev Gastroenterol Hepatol (2011) 5:201-12. doi:10.1586/egh.11.6
45. Holsinger LDC, Dener J, Green M, Booth R, Dalrymple S. Efficacy of a reversible cathepsin B inhibitor in a rodent model of liver fibrosis and human pharmacokinetic profile. Hepatology (2010) 52:1128A.
46. Doyle PS, Zhou YM, Engel JC, Mckerrow JH. A cysteine protease inhibitor cures Chagas' disease in an immunodeficient-mouse model of infection. Antimicrob Agents Chemother (2007) 51:3932-9. doi:10.1128/AAC.00436-07
47. Knoblach SM, Faden AI. Proteases in traumatic brain injury. In: Lendeckel U, Hooper NM, editors. Proteases in the Brain. Springer (2005).
48. Hook GR, Yu J, Sipes N, Pierschbacher MD, Hook V, Kindy MS. The cysteine protease cathepsin B is a key drug target and cysteine protease inhibitors are potential therapeutics for traumatic brain injury. J Neurotrauma (2014) 31:515-29. doi:10.1089/neu.2013.2944
49. Diaz-Arrastia R, Kochanek PM, Bergold P, Kenney K, Marx C, Grimes J, et al. Pharmacotherapy of traumatic brain injury: state of the science and the road forward report of the Department of Defense Neurotrauma Pharmacology Workgroup. J Neurotrauma (2013) 31(2):135-58. doi:10.1089/neu.2013.3019
50. Kabadi SV, Faden AI. Neuroprotective strategies for traumatic brain injury: improving clinical translation. Int J Mol Sci (2014) 15:1216-36. doi:10.3390/ijms15011216
51. Stocchetti N, Taccone FS, Citerio G, Pepe PE, Le Roux PD, Oddo M, et al. Neuroprotection in acute brain injury: an up-to-date review. Crit Care (2015) 19:186. doi:10.1186/s13054-015-0887-8
52. Fruton JS, Bergmann M. On the proteolytic enzymes of animal tissues: beef spleen. J Biol Chem (1939) 130:19-27.
53. Fruton JS, Irving GW, Bergmann M. One the proteolytic enzymes of beef spleen, beef kidney, and swine kidney. Classification of the cathepsins. J Biol Chem (1941) 138:249-62.
54. Tallan HH, Jones ME, Fruton JS. On the proteolytic enzymes of animal tissues. X. Beef spleen cathepsin C. J Biol Chem (1952) 194:793-805.
55. Greenbaum LM, Fruton JS. Purification and properties of beef spleen cathepsin B. J Biol Chem (1957) 226:173-80.
56. Takio K, Towatari T, Katunuma N, Teller DC, Titani K. Homology of amino acid sequences of rat liver cathepsins B and H with that of papain. Proc Natl Acad Sci U S A (1983) 80:3666-70. doi:10.1073/pnas.80.12.3666
57. Chan SJ, San Segundo B, Mccormick MB, Steiner DF. Nucleotide and predicted amino acid sequences of cloned human and mouse preprocathepsin B cDNAs. Proc Natl Acad Sci U S A (1986) 83:7721-5. doi:10.1073/pnas.83.20.7721
58. Musil D, Zucic D, Turk D, Engh RA, Mayr I, Huber R, et al. The refined 2.15 A X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity. EMBO J (1991) 10:2321-30.
59. Deussing J, Roth W, Saftig P, Peters C, Ploegh HL, Villadangos JA. Cathepsins B and D are dispensable for major histocompatibility complex class II-mediated antigen presentation. Proc Natl Acad Sci U S A (1998) 95:4516-21. doi:10.1073/pnas.95.8.4516
60. Mort JS. 333. Cathepsin B. Second ed. In: Barrett AJ, Rawlings ND, Woessner JF, editors. Handbook of Proteolytic Enzymes. Amsterdam: Elsevier Academic Press (2004) 1079-86.
61. Aronson NN Jr, Barrett AJ. The specificity of cathepsin B. Hydrolysis of glucagon at the C-terminus by a peptidyldipeptidase mechanism. Biochem J (1978) 171:759-65.
62. Takahashi T, Dehdarani AH, Yonezawa S, Tang J. Porcine spleen cathepsin B is an exopeptidase. J Biol Chem (1986) 261:9375-81.
63. Illy C, Quraishi O, Wang J, Purisima E, Vernet T, Mort JS. Role of the occluding loop in cathepsin B activity. J Biol Chem (1997) 272:1197-202. doi:10.1074/jbc.272.2.1197
64. Schechter I, Berger A. On the size of the active site in proteases. I. Papain. Biochem Biophys Res Commun (1967) 27:157-62. doi:10.1016/S0006-291X(67)80055-X
65. Gosalia DN, Salisbury CM, Ellman JA, Diamond SL. High throughput substrate specificity profiling of serine and cysteine proteases using solution-phase fluorogenic peptide microarrays. Mol Cell Proteomics (2005) 4:626-36. doi:10.1074/mcp.M500004-MCP200
66. Choe Y, Leonetti F, Greenbaum DC, Lecaille F, Bogyo M, Bromme D, et al. Substrate profiling of cysteine proteases using a combinatorial peptide library identifies functionally unique specificities. J Biol Chem (2006) 281:12824-32. doi:10.1074/jbc.M513331200
67. Barrett A, Rawlings N, Woessner J. Handbook of Proteolytic Enzymes. Amsterdam: Elsevier Academic Press (2004).
68. Schechter I, Berger A. On the active site of proteases. 3. Mapping the active site of papain; specific peptide inhibitors of papain. Biochem Biophys Res Commun (1968) 32:898-902. doi:10.1016/0006-291X(68)90326-4
69. Hook V, Schechter I, Demuth HU, Hook G. Alternative pathways for production of beta-amyloid peptides of Alzheimer's disease. Biol Chem (2008) 389:993-1006. doi:10.1515/BC.2008.124
70. Turk V, Stoka V, Vasiljeva O, Renko M, Sun T, Turk B, et al. Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochim Biophys Acta (2012) 1824:68-88. doi:10.1016/j.bbapap.2011.10.002
71. Rossi A, Deveraux Q, Turk B, Sali A. Comprehensive search for cysteine cathepsins in the human genome. Biol Chem (2004) 385:363-72. doi:10.1515/BC.2004.040
72. Fong D, Chan MM, Hsieh WT, Menninger JC, Ward DC. Confirmation of the human cathepsin B gene (CTSB) assignment to chromosome 8. Hum Genet (1992) 89:10-2. doi:10.1007/BF00207033
73. Berquin IM, Cao L, Fong D, Sloane BF. Identification of two new exons and multiple transcription start points in the 5'-untranslated region of the human cathepsin-B-encoding gene. Gene (1995) 159:143-9. doi:10.1016/0378-1119(95)00072-E
74. Gong Q, Chan SJ, Bajkowski AS, Steiner DF, Frankfater A. Characterization of the cathepsin B gene and multiple mRNAs in human tissues: evidence for alternative splicing of cathepsin B pre-mRNA. DNA Cell Biol (1993) 12:299-309. doi:10.1089/dna.1993.12.299
75. Tabares-Seisdedos R, Rubenstein JL. Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer. Mol Psychiatry (2009) 14:563-89. doi:10.1038/mp.2009.2
76. Mahurkar S, Idris MM, Reddy DN, Bhaskar S, Rao GV, Thomas V, et al. Association of cathepsin B gene polymorphisms with tropical calcific pancreatitis. Gut (2006) 55:1270-5. doi:10.1136/gut.2005.087403
77. Qian F, Frankfater A, Chan SJ, Steiner DF. The structure of the mouse cathepsin B gene and its putative promoter. DNA Cell Biol (1991) 10:159-68. doi:10.1089/dna.1991.10.159
78. Deussing J, Roth W, Rommerskirch W, Wiederanders B, Von Figura K, Peters C. The genes of the lysosomal cysteine proteinases cathepsin B, H, L, and S map to different mouse chromosomes. Mamm Genome (1997) 8:241-5. doi:10.1007/s003359900401
79. Sivaparvathi M, Sawaya R, Wang SW, Rayford A, Yamamoto M, Liotta LA, et al. Overexpression and localization of cathepsin B during the progression of human gliomas. Clin Exp Metastasis (1995) 13:49-56. doi:10.1007/BF00144018
80. Carthew RW, Sontheimer EJ. Origins and mechanisms of miRNAs and siRNAs. Cell (2009) 136:642-55. doi:10.1016/j.cell.2009.01.035
81. Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V. Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol (2004) 5:R13. doi:10.1186/gb-2004-5-3-r13
82. Bhalala OG, Srikanth M, Kessler JA. The emerging roles of microRNAs in CNS injuries. Nat Rev Neurol (2013) 9:328-39. doi:10.1038/nrneurol.2013.67
83. Redell JB, Liu Y, Dash PK. Traumatic brain injury alters expression of hippocampal microRNAs: potential regulators of multiple pathophysiological processes. J Neurosci Res (2009) 87:1435-48. doi:10.1002/jnr.21945
84. Venkataraman S, Birks DK, Balakrishnan I, Alimova I, Harris PS, Patel PR, et al. MicroRNA 218 acts as a tumor suppressor by targeting multiple cancer phenotype-associated genes in medulloblastoma. J Biol Chem (2013) 288:1918-28. doi:10.1074/jbc.M112.396762
85. Tiribuzi R, Crispoltoni L, Porcellati S, Di Lullo M, Florenzano F, Pirro M, et al. miR128 up-regulation correlates with impaired amyloid beta(1-42) degradation in monocytes from patients with sporadic Alzheimer's disease. Neurobiol Aging (2014) 35:345-56. doi:10.1016/j.neurobiolaging.2013.08.003
86. Wulczyn FG, Smirnova L, Rybak A, Brandt C, Kwidzinski E, Ninnemann O, et al. Post-transcriptional regulation of the let-7 microRNA during neural cell specification. FASEB J (2007) 21:415-26. doi:10.1096/fj.06-6130com
87. Katunuma N. Posttranslational processing and modification of cathepsins and cystatins. J Signal Transduct (2010) 2010:375345. doi:10.1155/2010/375345
88. Turk B, Turk D, Turk V. Lysosomal cysteine proteases: more than scavengers. Biochim Biophys Acta (2000) 1477:98-111. doi:10.1016/S0167-4838(99)00263-0
89. Neurath H. Evolution of proteolytic enzymes. Science (1984) 224:350-7. doi:10.1126/science.6369538
90. Pungercar JR, Caglic D, Sajid M, Dolinar M, Vasiljeva O, Pozgan U, et al. Autocatalytic processing of procathepsin B is triggered by proenzyme activity. FEBS J (2009) 276:660-8. doi:10.1111/j.1742-4658.2008.06815.x
91. Mach L, Mort JS, Glossl J. Maturation of human procathepsin B. Proenzyme activation and proteolytic processing of the precursor to the mature proteinase, in vitro, are primarily unimolecular processes. J Biol Chem (1994) 269:13030-5.
92. Kominami E, Tsukahara T, Bando Y, Katunuma N. Autodegradation of lysosomal cysteine proteinases. Biochem Biophys Res Commun (1987) 144:749-56. doi:10.1016/S0006-291X(87)80028-1
93. Natale JE, Ahmed F, Cernak I, Stoica B, Faden AI. Gene expression profile changes are commonly modulated across models and species after traumatic brain injury. J Neurotrauma (2003) 20:907-27. doi:10.1089/089771503770195777
94. Luo CL, Chen XP, Yang R, Sun YX, Li QQ, Bao HJ, et al. Cathepsin B contributes to traumatic brain injury-induced cell death through a mitochondria-mediated apoptotic pathway. J Neurosci Res (2010) 88:2847-58. doi:10.1002/jnr.22453
95. Zhang M, Shan H, Chang P, Wang T, Dong W, Chen X, et al. Hydrogen sulfide offers neuroprotection on traumatic brain injury in parallel with reduced apoptosis and autophagy in mice. PLoS One (2014) 9:e87241. doi:10.1371/journal.pone.0087241
96. Zhang YB, Chen XP, Tao LY, Qin ZH, Li SX, Yang L, et al. Expression of cathepsin-B and-D in rat's brain after traumatic brain injury. Fa Yi Xue Za Zhi (2006) 22(404-6):410.
97. Martinez-Vargas M, Soto-Nunez M, Tabla-Ramon E, Solis B, Gonzalez-Rivera R, Perez-Arredondo A, et al. Cystatin C has a dual role in post-traumatic brain injury recovery. Int J Mol Sci (2014) 15:5807-20. doi:10.3390/ijms15045807
98. Sun YX, Dai DK, Liu R, Wang T, Luo CL, Bao HJ, et al. Therapeutic effect of SN50, an inhibitor of nuclear factor-kappaB, in treatment of TBI in mice. Neurol Sci (2013) 34:345-55. doi:10.1007/s10072-012-1007-z
99. Ellis RC, Earnhardt JN, Hayes RL, Wang KK, Anderson DK. Cathepsin B mRNA and protein expression following contusion spinal cord injury in rats. J Neurochem (2004) 88:689-97. doi:10.1046/j.1471-4159.2003.02197.x
100. Ellis RC, O'steen WA, Hayes RL, Nick HS, Wang KK, Anderson DK. Cellular localization and enzymatic activity of cathepsin B after spinal cord injury in the rat. Exp Neurol (2005) 193:19-28. doi:10.1016/j.expneurol.2004.11.034
101. Vreemann A, Qu H, Mayer K, Andersen LB, Stefana MI, Wehner S, et al. Cathepsin B release from rodent intestine mucosa due to mechanical injury results in extracellular matrix damage in early post-traumatic phases. Biol Chem (2009) 390:481-92. doi:10.1515/BC.2009.055
102. Yu ZQ, Jia Y, Chen G. Possible involvement of cathepsin B/D and caspase-3 in deferoxamine-related neuroprotection of early brain injury after subarachnoid haemorrhage in rats. Neuropathol Appl Neurobiol (2014) 40:270-83. doi:10.1111/nan.12091
103. Wang Y, Gao A, Xu X, Dang B, You W, Li H, et al. The neuroprotection of lysosomotropic agents in experimental subarachnoid hemorrhage probably involving the apoptosis pathway triggering by cathepsins via chelating intralysosomal iron. Mol Neurobiol (2014) 52(1):64-77. doi:10.1007/s12035-014-8846-y
104. Aoki T, Kataoka H, Ishibashi R, Nozaki K, Hashimoto N. Cathepsin B, K, and S are expressed in cerebral aneurysms and promote the progression of cerebral aneurysms. Stroke (2008) 39:2603-10. doi:10.1161/STROKEAHA.107.513648
105. Yamada E, Chue CH, Yukioka N, Hazama F. Causative role of lysosomal enzymes in the pathogenesis of cerebral lesions due to brain edema under chronic hypertension. Acta Neurochir Suppl (Wien) (1994) 60:83-5.
106. Tsubokawa T, Yamaguchi-Okada M, Calvert JW, Solaroglu I, Shimamura N, Yata K, et al. Neurovascular and neuronal protection by E64d after focal cerebral ischemia in rats. J Neurosci Res (2006) 84:832-40. doi:10.1002/jnr.20977
107. Seyfried D, Han Y, Zheng Z, Day N, Moin K, Rempel S, et al. Cathepsin B and middle cerebral artery occlusion in the rat. J Neurosurg (1997) 87:716-23. doi:10.3171/jns.1997.87.5.0716
108. Yamashima T, Kohda Y, Tsuchiya K, Ueno T, Yamashita J, Yoshioka T, et al. Inhibition of ischaemic hippocampal neuronal death in primates with cathepsin B inhibitor CA-074: a novel strategy for neuroprotection based on 'calpain-cathepsin hypothesis'. Eur J Neurosci (1998) 10:1723-33. doi:10.1046/j.1460-9568.1998.00184.x
109. Tsuchiya K, Kohda Y, Yoshida M, Zhao L, Ueno T, Yamashita J, et al. Postictal blockade of ischemic hippocampal neuronal death in primates using selective cathepsin inhibitors. Exp Neurol (1999) 155:187-94. doi:10.1006/exnr.1998.6988
110. Anagli J, Abounit K, Stemmer P, Han Y, Allred L, Weinsheimer S, et al. Effects of cathepsins B and L inhibition on postischemic protein alterations in the brain. Biochem Biophys Res Commun (2008) 366:86-91. doi:10.1016/j.bbrc.2007.11.104
111. Ni H, Yan JZ, Zhang LL, Feng X, Wu XR. Long-term effects of recurrent neonatal seizures on neurobehavioral function and related gene expression and its intervention by inhibitor of cathepsin B. Neurochem Res (2012) 37:31-9. doi:10.1007/s11064-011-0578-z
112. Wang Y, Gu ZL, Cao Y, Liang ZQ, Han R, Bennett MC, et al. Lysosomal enzyme cathepsin B is involved in kainic acid-induced excitotoxicity in rat striatum. Brain Res (2006) 1071:245-9. doi:10.1016/j.brainres.2005.10.074
113. Ruff RL, Secrist D. Inhibitors of prostaglandin synthesis or cathepsin B prevent muscle wasting due to sepsis in the rat. J Clin Invest (1984) 73:1483-6. doi:10.1172/JCI111352
114. Hummel RP III, James JH, Warner BW, Hasselgren PO, Fischer JE. Evidence that cathepsin B contributes to skeletal muscle protein breakdown during sepsis. Arch Surg (1988) 123:221-4. doi:10.1001/archsurg.1988.01400260105013
115. Sun L, Wu Z, Hayashi Y, Peters C, Tsuda M, Inoue K, et al. Microglial cathepsin B contributes to the initiation of peripheral inflammation-induced chronic pain. J Neurosci (2012) 32:11330-42. doi:10.1523/JNEUROSCI.0677-12.2012
116. Terada K, Yamada J, Hayashi Y, Wu Z, Uchiyama Y, Peters C, et al. Involvement of cathepsin B in the processing and secretion of interleukin-1beta in chromogranin A-stimulated microglia. Glia (2010) 58:114-24. doi:10.1002/glia.20906
117. Offen D, Barhum Y, Melamed E, Embacher N, Schindler C, Ransmayr G. Spinal cord mRNA profile in patients with ALS: comparison with transgenic mice expressing the human SOD-1 mutant. J Mol Neurosci (2009) 38:85-93. doi:10.1007/s12031-007-9004-z
118. Ferraiuolo L, Heath PR, Holden H, Kasher P, Kirby J, Shaw PJ. Microarray analysis of the cellular pathways involved in the adaptation to and progression of motor neuron injury in the SOD1 G93A mouse model of familial ALS. J Neurosci (2007) 27:9201-19. doi:10.1523/JNEUROSCI.1470-07.2007
119. Bouter Y, Kacprowski T, Weissmann R, Dietrich K, Borgers H, Brauss A, et al. Deciphering the molecular profile of plaques, memory decline and neuron loss in two mouse models for Alzheimer's disease by deep sequencing. Front Aging Neurosci (2014) 6:75. doi:10.3389/fnagi.2014.00075
120. Sun Y, Rong X, Lu W, Peng Y, Li J, Xu S, et al. Translational study of Alzheimer's disease (AD) biomarkers from brain tissues in AbetaPP/PS1 mice and serum of AD patients. J Alzheimers Dis (2015) 45:269-82. doi:10.3233/JAD-142805
121. Saris CG, Groen EJ, Koekkoek JA, Veldink JH, Van Den Berg LH. Meta-analysis of gene expression profiling in amyotrophic lateral sclerosis: a comparison between transgenic mouse models and human patients. Amyotroph Lateral Scler Frontotemporal Degener (2013) 14:177-89. doi:10.3109/21678421.2012.729842
122. Ni H, Ren SY, Zhang LL, Sun Q, Tian T, Feng X. Expression profiles of hippocampal regenerative sprouting-related genes and their regulation by E-64d in a developmental rat model of penicillin-induced recurrent epilepticus. Toxicol Lett (2013) 217:162-9. doi:10.1016/j.toxlet.2012.12.010
123. Assfalg-Machleidt I, Jochum M, Nast-Kolb D, Siebeck M, Billing A, Joka T, et al. Cathepsin B-indicator for the release of lysosomal cysteine proteinases in severe trauma and inflammation. Biol Chem Hoppe Seyler (1990) 371(Suppl):211-22.
124. Jochum M, Machleidt W, Fritz H. Phagocyte proteinases in multiple trauma and sepsi: pathomechanims and related therapeutic approaches. In: Neugebauer EA, Holaday JW, editors. Handbook of Mediators in Septic Shock. CRC Press (1993). p. 335-61.
125. Nagai A, Murakawa Y, Terashima M, Shimode K, Umegae N, Takeuchi H, et al. Cystatin C and cathepsin B in CSF from patients with inflammatory neurologic diseases. Neurology (2000) 55:1828-32. doi:10.1212/WNL.55.12.1828
126. Bever CT Jr, Garver DW. Increased cathepsin B activity in multiple sclerosis brain. J Neurol Sci (1995) 131:71-3. doi:10.1016/0022-510X(95)00039-5
127. Dangond F, Hwang D, Camelo S, Pasinelli P, Frosch MP, Stephanopoulos G, et al. Molecular signature of late-stage human ALS revealed by expression profiling of postmortem spinal cord gray matter. Physiol Genomics (2004) 16:229-39. doi:10.1152/physiolgenomics.00087.2001
128. Kikuchi H, Yamada T, Furuya H, Doh-Ura K, Ohyagi Y, Iwaki T, et al. Involvement of cathepsin B in the motor neuron degeneration of amyotrophic lateral sclerosis. Acta Neuropathol (2003) 105:462-8. doi:10.1007/s00401-002-0667-9
129. Cataldo AM, Nixon RA. Enzymatically active lysosomal proteases are associated with amyloid deposits in Alzheimer brain. Proc Natl Acad Sci U S A (1990) 87:3861-5. doi:10.1073/pnas.87.10.3861
130. Sundelof J, Sundstrom J, Hansson O, Eriksdotter-Jonhagen M, Giedraitis V, Larsson A, et al. Higher cathepsin B levels in plasma in Alzheimer's disease compared to healthy controls. J Alzheimers Dis (2010) 22:1223-30. doi:10.3233/JAD-2010-101023
131. Zhang J, Goodlett DR, Quinn JF, Peskind E, Kaye JA, Zhou Y, et al. Quantitative proteomics of cerebrospinal fluid from patients with Alzheimer disease. J Alzheimers Dis (2005) 7:125-33.
132. Armstrong A, Mattsson N, Appelqvist H, Janefjord C, Sandin L, Agholme L, et al. Lysosomal network proteins as potential novel CSF biomarkers for Alzheimer's disease. Neuromolecular Med (2014) 16:150-60. doi:10.1007/s12017-013-8269-3
133. Trabandt A, Gay RE, Fassbender HG, Gay S. Cathepsin B in synovial cells at the site of joint destruction in rheumatoid arthritis. Arthritis Rheum (1991) 34:1444-51. doi:10.1002/art.1780341116
134. Baici A, Lang A, Horler D, Kissling R, Merlin C. Cathepsin B in osteoarthritis: cytochemical and histochemical analysis of human femoral head cartilage. Ann Rheum Dis (1995) 54:289-97. doi:10.1136/ard.54.4.281
135. Menzel K, Hausmann M, Obermeier F, Schreiter K, Dunger N, Bataille F, et al. Cathepsins B, L and D in inflammatory bowel disease macrophages and potential therapeutic effects of cathepsin inhibition in vivo. Clin Exp Immunol (2006) 146:169-80. doi:10.1111/j.1365-2249.2006.03188.x
136. Reinheckel T, Deussing J, Roth W, Peters C. Towards specific functions of lysosomal cysteine peptidases: phenotypes of mice deficient for cathepsin B or cathepsin L. Biol Chem (2001) 382:735-41. doi:10.1515/BC.2001.089
137. Friedrichs B, Tepel C, Reinheckel T, Deussing J, Von Figura K, Herzog V, et al. Thyroid functions of mouse cathepsins B, K, and L. J Clin Invest (2003) 111:1733-45. doi:10.1172/JCI15990
138. Houseweart MK, Pennacchio LA, Vilaythong A, Peters C, Noebels JL, Myers RM. Cathepsin B but not cathepsins L or S contributes to the pathogenesis of Unverricht-Lundborg progressive myoclonus epilepsy (EPM1). J Neurobiol (2003) 56:315-27. doi:10.1002/neu.10253
139. Hook VY, Kindy M, Reinheckel T, Peters C, Hook G. Genetic cathepsin B deficiency reduces beta-amyloid in transgenic mice expressing human wild-type amyloid precursor protein. Biochem Biophys Res Commun (2009) 386:284-8. doi:10.1016/j.bbrc.2009.05.131
140. Kindy MS, Yu J, Zhu H, El-Amouri SS, Hook V, Hook GR. Deletion of the cathepsin B gene improves memory deficits in a transgenic alzheimer's disease mouse model expressing AbetaPP containing the wild-type beta-secretase site sequence. J Alzheimers Dis (2012) 29:827-40. doi:10.3233/JAD-2012-111604
141. Hook G, Yu J, Toneff T, Kindy M, Hook V. Brain pyroglutamate amyloid-beta is produced by cathepsin B and is reduced by the cysteine protease inhibitor E64d, representing a potential Alzheimer's disease therapeutic. J Alzheimers Dis (2014) 41:129-49. doi:10.3233/JAD-131370
142. Mueller-Steiner S, Zhou Y, Arai H, Roberson ED, Sun B, Chen J, et al. Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease. Neuron (2006) 51:703-14. doi:10.1016/j.neuron.2006.07.027
143. Wu Z, Sun L, Hashioka S, Yu S, Schwab C, Okada R, et al. Differential pathways for interleukin-1beta production activated by chromogranin A and amyloid beta in microglia. Neurobiol Aging (2013) 34:2715-25. doi:10.1016/j.neurobiolaging.2013.05.018
144. Ha SD, Martins A, Khazaie K, Han J, Chan BM, Kim SO. Cathepsin B is involved in the trafficking of TNF-alpha-containing vesicles to the plasma membrane in macrophages. J Immunol (2008) 181:690-7. doi:10.4049/jimmunol.181.1.690
145. Guicciardi ME, Bronk SF, Werneburg NW, Yin XM, Gores GJ. Bid is upstream of lysosome-mediated caspase 2 activation in tumor necrosis factor alpha-induced hepatocyte apoptosis. Gastroenterology (2005) 129:269-84. doi:10.1053/j.gastro.2005.05.022
146. Allan ER, Yates RM. Redundancy between cysteine cathepsins in murine experimental autoimmune encephalomyelitis. PLoS One (2015) 10:e0128945. doi:10.1371/journal.pone.0128945
147. Jawhar S, Wirths O, Bayer TA. Pyroglutamate amyloid-beta (Abeta): a hatchet man in Alzheimer disease. J Biol Chem (2011) 286:38825-32. doi:10.1074/jbc.R111.288308
148. Hook V, Toneff T, Bogyo M, Medzihradszky KF, Nevenu J, Lane W, et al. Inhibition of cathepsin B reduces β-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: evidence for cathepsin B as a candidate β-secretase of Alzheimer's disease. Biol Chem (2005) 386:931-40. doi:10.1515/BC.2005.108
149. Hook V, Kindy M, Hook G. Cysteine protease inhibitors effectively reduce in vivo levels of brain beta-amyloid related to Alzheimer's disease. Biol Chem (2007) 388:247-52. doi:10.1515/BC.2007.027
150. Hook G, Hook VY, Kindy M. Cysteine protease inhibitors reduce brain beta-amyloid and beta-secretase activity in vivo and are potential Alzheimer's disease therapeutics. Biol Chem (2007) 388:979-83. doi:10.1515/BC.2007.027
151. Hook VY, Kindy M, Hook G. Inhibitors of cathepsin B improve memory and reduce Abeta in transgenic Alzheimer's Disease mice expressing the wild-type, but not the Swedish mutant, beta-secretase APP site. J Biol Chem (2008) 283:7745-53. doi:10.1074/jbc.M708362200
152. Roberts GW, Gentleman SM, Lynch A, Murray L, Landon M, Graham DI. Beta amyloid protein deposition in the brain after severe head injury: implications for the pathogenesis of Alzheimer's disease. J Neurol Neurosurg Psychiatry (1994) 57:419-25. doi:10.1136/jnnp.57.4.419
153. Chen XH, Johnson VE, Uryu K, Trojanowski JQ, Smith DH. A lack of amyloid beta plaques despite persistent accumulation of amyloid beta in axons of long-term survivors of traumatic brain injury. Brain Pathol (2009) 19:214-23. doi:10.1111/j.1750-3639.2008.00176.x
154. Hernandez-Ontiveros DG, Tajiri N, Acosta S, Giunta B, Tan J, Borlongan CV. Microglia activation as a biomarker for traumatic brain injury. Front Neurol (2013) 4:30. doi:10.3389/fneur.2013.00030
155. Yatsiv I, Morganti-Kossmann MC, Perez D, Dinarello CA, Novick D, Rubinstein M, et al. Elevated intracranial IL-18 in humans and mice after traumatic brain injury and evidence of neuroprotective effects of IL-18-binding protein after experimental closed head injury. J Cereb Blood Flow Metab (2002) 22:971-8. doi:10.1097/00004647-200208000-00008
156. Kamm K, Vanderkolk W, Lawrence C, Jonker M, Davis AT. The effect of traumatic brain injury upon the concentration and expression of interleukin-1beta and interleukin-10 in the rat. J Trauma (2006) 60:152-7. doi:10.1097/01.ta.0000196345.81169.a1
157. de Rivero Vaccari JP, Dietrich WD, Keane RW. Activation and regulation of cellular inflammasomes: gaps in our knowledge for central nervous system injury. J Cereb Blood Flow Metab (2014) 34:369-75. doi:10.1038/jcbfm.2013.227
158. Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol (2008) 9:857-65. doi:10.1038/ni.1636
159. Salvesen GS. A lysosomal protease enters the death scene. J Clin Invest (2001) 107:21-2. doi:10.1172/JCI11829
160. Goodman JC, Robertson CS, Grossman RG, Narayan RK. Elevation of tumor necrosis factor in head injury. J Neuroimmunol (1990) 30:213-7. doi:10.1016/0165-5728(90)90105-V
161. Guicciardi ME, Deussing J, Miyoshi H, Bronk SF, Svingen PA, Peters C, et al. Cathepsin B contributes to TNF-alpha-mediated hepatocyte apoptosis by promoting mitochondrial release of cytochrome c. J Clin Invest (2000) 106:1127-37. doi:10.1172/JCI9914
162. Felbor U, Kessler B, Mothes W, Goebel HH, Ploegh HL, Bronson RT, et al. Neuronal loss and brain atrophy in mice lacking cathepsins B and L. Proc Natl Acad Sci U S A (2002) 99:7883-8. doi:10.1073/pnas.112632299
163. Sevenich L, Pennacchio LA, Peters C, Reinheckel T. Human cathepsin L rescues the neurodegeneration and lethality in cathepsin B/L double-deficient mice. Biol Chem (2006) 387:885-91. doi:10.1515/BC.2006.112
164. Howie AJ, Burnett D, Crocker J. The distribution of cathepsin B in human tissues. J Pathol (1985) 145:307-14. doi:10.1002/path.1711450404
165. Kominami E, Tsukahara T, Bando Y, Katunuma N. Distribution of cathepsins B and H in rat tissues and peripheral blood cells. J Biochem (1985) 98:87-93.
166. San Segundo B, Chan SJ, Steiner DF. Differences in cathepsin B mRNA levels in rat tissues suggest specialized functions. FEBS Lett (1986) 201:251-6. doi:10.1016/0014-5793(86)80618-4
167. Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A, et al. Proteomics. Tissue-based map of the human proteome. Science (2015) 347:1260419. doi:10.1126/science.1260419
168. Bernstein HG, Kirschke H, Wiederanders B, Kloss P, Rinne A, Dorn A. Cathepsin B immunoreactivity is widely distributed in the rat brain. J Hirnforsch (1988) 29:17-9.
169. Bernstein HG, Kirschke H, Wiederanders B, Schmidt D, Rinne A. Antigenic expression of cathepsin B in aged human brain. Brain Res Bull (1990) 24:543-9. doi:10.1016/0361-9230(90)90157-U
170. Nakamura Y, Takeda M, Suzuki H, Hattori H, Tada K, Hariguchi S, et al. Abnormal distribution of cathepsins in the brain of patients with Alzheimer's disease. Neurosci Lett (1991) 130:195-8. doi:10.1016/0304-3940(91)90395-A
171. Ii K, Ito H, Kominami E, Hirano A. Abnormal distribution of cathepsin proteinases and endogenous inhibitors (cystatins) in the hippocampus of patients with Alzheimer's disease, parkinsonism-dementia complex on Guam, and senile dementia and in the aged. Virchows Arch A Pathol Anat Histopathol (1993) 423:185-94. doi:10.1007/BF01614769
172. Bernstein HG, Sormunen R, Jarvinen M, Kloss P, Kirschke H, Rinne A. Cathepsin B immunoreactive neurons in rat brain. A combined light and electron microscopic study. J Hirnforsch (1989) 30:313-7.
173. Jung H, Lee EY, Lee SI. Age-related changes in ultrastructural features of cathepsin B-and D-containing neurons in rat cerebral cortex. Brain Res (1999) 844:43-54. doi:10.1016/S0006-8993(99)01888-0
174. Petanceska S, Burke S, Watson SJ, Devi L. Differential distribution of messenger RNAs for cathepsins B, L and S in adult rat brain: an in situ hybridization study. Neuroscience (1994) 59:729-38. doi:10.1016/0306-4522(94)90190-2
175. Nilsson E, Bodolea C, Gordh T, Larsson A. Cerebrospinal fluid cathepsin B and S. Neurol Sci (2013) 34:445-8. doi:10.1007/s10072-012-1022-0
176. Nakanishi H, Tominaga K, Amano T, Hirotsu I, Inoue T, Yamamoto K. Age-related changes in activities and localizations of cathepsins D, E, B, and L in the rat brain tissues. Exp Neurol (1994) 126:119-28. doi:10.1006/exnr.1994.1048
177. de Duve C. Lysosomes revisited. Eur J Biochem (1983) 137:391-7. doi:10.1111/j.1432-1033.1983.tb07841.x
178. Mortimore GE, Lardeux BR, Adams CE. Regulation of microautophagy and basal protein turnover in rat liver. Effects of short-term starvation. J Biol Chem (1988) 263:2506-12.
179. Bohley P, Seglen PO. Proteases and proteolysis in the lysosome. Experientia (1992) 48:151-7. doi:10.1007/BF01923508
180. Dean RT, Barrett AJ. Lysosomes. Essays Biochem (1976) 12:1-40.
181. Bromme D, Bonneau PR, Lachance P, Storer AC. Engineering the S2 subsite specificity of human cathepsin S to a cathepsin L-and cathepsin B-like specificity. J Biol Chem (1994) 269:30238-42.
182. Blott EJ, Griffiths GM. Secretory lysosomes. Nat Rev Mol Cell Biol (2002) 3:122-31. doi:10.1038/nrm732
183. Zhang Z, Chen G, Zhou W, Song A, Xu T, Luo Q, et al. Regulated ATP release from astrocytes through lysosome exocytosis. Nat Cell Biol (2007) 9:945-53. doi:10.1038/ncb1620
184. Verderio C, Cagnoli C, Bergami M, Francolini M, Schenk U, Colombo A, et al. TI-VAMP/VAMP7 is the SNARE of secretory lysosomes contributing to ATP secretion from astrocytes. Biol Cell (2012) 104:213-28. doi:10.1111/boc.201100070
185. Spizz G, Blackshear PJ. Identification and characterization of cathepsin B as the cellular MARCKS cleaving enzyme. J Biol Chem (1997) 272:23833-42. doi:10.1074/jbc.272.38.23833
186. Graber S, Maiti S, Halpain S. Cathepsin B-like proteolysis and MARCKS degradation in sub-lethal NMDA-induced collapse of dendritic spines. Neuropharmacology (2004) 47:706-13. doi:10.1016/j.neuropharm.2004.08.004
187. Kopitar-Jerala N, Turk B. Cleavage of the myristoylated alanine-rich C kinase substrate (MARCKS) by cysteine cathepsins in cells and tissues of stefin B-deficient mice. Biol Chem (2007) 388:847-52. doi:10.1515/BC.2007.092
188. Linke M, Herzog V, Brix K. Trafficking of lysosomal cathepsin B-green fluorescent protein to the surface of thyroid epithelial cells involves the endosomal/lysosomal compartment. J Cell Sci (2002) 115:4877-89. doi:10.1242/jcs.00184
189. Pozuelo-Rubio M. 14-3-3zeta binds class III phosphatidylinositol-3-kinase and inhibits autophagy. Autophagy (2011) 7:240-2. doi:10.4161/auto.7.2.14286
190. Brix K, Mcinnes J, Al-Hashimi A, Rehders M, Tamhane T, Haugen MH. Proteolysis mediated by cysteine cathepsins and legumain-recent advances and cell biological challenges. Protoplasma (2015) 252:755-74. doi:10.1007/s00709-014-0730-0
191. Kelly RB. Pathways of protein secretion in eukaryotes. Science (1985) 230:25-32. doi:10.1126/science.2994224
192. Kukor Z, Mayerle J, Kruger B, Toth M, Steed PM, Halangk W, et al. Presence of cathepsin B in the human pancreatic secretory pathway and its role in trypsinogen activation during hereditary pancreatitis. J Biol Chem (2002) 277:21389-96. doi:10.1074/jbc.M200878200
193. Halangk W, Lerch MM, Brandt-Nedelev B, Roth W, Ruthenbuerger M, Reinheckel T, et al. Role of cathepsin B in intracellular trypsinogen activation and the onset of acute pancreatitis. J Clin Invest (2000) 106:773-81. doi:10.1172/JCI9411
194. Kuliawat R, Klumperman J, Ludwig T, Arvan P. Differential sorting of lysosomal enzymes out of the regulated secretory pathway in pancreatic beta-cells. J Cell Biol (1997) 137:595-608. doi:10.1083/jcb.137.3.595
195. Shinagawa T, Nakayama K, Uchiyama Y, Kominami E, Doi Y, Hashiba K, et al. Role of cathepsin B as prorenin processing enzyme in human kidney. Hypertens Res (1995) 18:131-6. doi:10.1291/hypres.18.131
196. Turk B, Dolenc I, Zerovnik E, Turk D, Gubensek F, Turk V. Human cathepsin B is a metastable enzyme stabilized by specific ionic interactions associated with the active site. Biochemistry (1994) 33:14800-6. doi:10.1021/bi00253a019
197. Pratt MR, Sekedat MD, Chiang KP, Muir TW. Direct measurement of cathepsin B activity in the cytosol of apoptotic cells by an activity-based probe. Chem Biol (2009) 16:1001-12. doi:10.1016/j.chembiol.2009.07.011
198. Polgar L, Csoma C. Dissociation of ionizing groups in the binding cleft inversely controls the endo-and exopeptidase activities of cathepsin B. J Biol Chem (1987) 262:14448-53.
199. Almeida PC, Nantes IL, Chagas JR, Rizzi CC, Faljoni-Alario A, Carmona E, et al. Cathepsin B activity regulation. Heparin-like glycosaminogylcans protect human cathepsin B from alkaline pH-induced inactivation. J Biol Chem (2001) 276:944-51. doi:10.1074/jbc.M003820200
200. Turk B, Dolenc I, Turk V, Bieth JG. Kinetics of the pH-induced inactivation of human cathepsin L. Biochemistry (1993) 32:375-80. doi:10.1021/bi00052a046
201. Turk B, Turk D, Salvesen GS. Regulating cysteine protease activity: essential role of protease inhibitors as guardians and regulators. Curr Pharm Des (2002) 8:1623-37. doi:10.2174/1381612023394124
202. Abrahamson M, Barrett AJ, Salvesen G, Grubb A. Isolation of six cysteine proteinase inhibitors from human urine. Their physicochemical and enzyme kinetic properties and concentrations in biological fluids. J Biol Chem (1986) 261:11282-9.
203. Sundelof J, Sundstrom J, Hansson O, Eriksdotter-Jonhagen M, Giedraitis V, Larsson A, et al. Cystatin C levels are positively correlated with both Abeta42 and tau levels in cerebrospinal fluid in persons with Alzheimer's disease, mild cognitive impairment, and healthy controls. J Alzheimers Dis (2010) 21:471-8. doi:10.3233/JAD-2010-091594
204. de Duve C, De Reuck AVS, Cameron MP, Ciba Foundation. Ciba Foundation Symposium: Lysosomes; [Proceedings]. Boston, MA: Little, Brown (1963).
205. Lafrenaye AD, Mcginn MJ, Povlishock JT. Increased intracranial pressure after diffuse traumatic brain injury exacerbates neuronal somatic membrane poration but not axonal injury: evidence for primary intracranial pressure-induced neuronal perturbation. J Cereb Blood Flow Metab (2012) 32:1919-32. doi:10.1038/jcbfm.2012.95
206. Luo CL, Chen XP, Li LL, Li QQ, Li BX, Xue AM, et al. Poloxamer 188 attenuates in vitro traumatic brain injury-induced mitochondrial and lysosomal membrane permeabilization damage in cultured primary neurons. J Neurotrauma (2013) 30:597-607. doi:10.1089/neu.2012.2425
207. Bao HJ, Wang T, Zhang MY, Liu R, Dai DK, Wang YQ, et al. Poloxamer-188 attenuates TBI-induced blood-brain barrier damage leading to decreased brain edema and reduced cellular death. Neurochem Res (2012) 37:2856-67. doi:10.1007/s11064-012-0880-4
208. Gu JH, Ge JB, Li M, Xu HD, Wu F, Qin ZH. Poloxamer 188 protects neurons against ischemia/reperfusion injury through preserving integrity of cell membranes and blood brain barrier. PLoS One (2013) 8:e61641. doi:10.1371/journal.pone.0061641
209. Amritraj A, Peake K, Kodam A, Salio C, Merighi A, Vance JE, et al. Increased activity and altered subcellular distribution of lysosomal enzymes determine neuronal vulnerability in Niemann-Pick type C1-deficient mice. Am J Pathol (2009) 175:2540-56. doi:10.2353/ajpath.2009.081096
210. Zhao S, Aviles ER Jr, Fujikawa DG. Nuclear translocation of mitochondrial cytochrome c, lysosomal cathepsins B and D, and three other death-promoting proteins within the first 60 minutes of generalized seizures. J Neurosci Res (2010) 88:1727-37. doi:10.1002/jnr.22338
211. Codolo G, Plotegher N, Pozzobon T, Brucale M, Tessari I, Bubacco L, et al. Triggering of inflammasome by aggregated alpha-synuclein, an inflammatory response in synucleinopathies. PLoS One (2013) 8:e55375. doi:10.1371/journal.pone.0055375
212. Freeman D, Cedillos R, Choyke S, Lukic Z, Mcguire K, Marvin S, et al. Alpha-synuclein induces lysosomal rupture and cathepsin dependent reactive oxygen species following endocytosis. PLoS One (2013) 8:e62143. doi:10.1371/journal.pone.0062143
213. Ditaranto K, Tekirian TL, Yang AJ. Lysosomal membrane damage in soluble Abeta-mediated cell death in Alzheimer's disease. Neurobiol Dis (2001) 8:19-31. doi:10.1006/nbdi.2000.0364
214. Aits S, Jaattela M. Lysosomal cell death at a glance. J Cell Sci (2013) 126:1905-12. doi:10.1242/jcs.091181
215. Yamashima T, Oikawa S. The role of lysosomal rupture in neuronal death. Prog Neurobiol (2009) 89:343-58. doi:10.1016/j.pneurobio.2009.09.003
216. Yamashima T. Reconsider Alzheimer's disease by the 'calpain-cathepsin hypothesis'-a perspective review. Prog Neurobiol (2013) 105:1-23. doi:10.1016/j.pneurobio.2013.02.004
217. Zhu H, Yoshimoto T, Yamashima T. Heat shock protein 70.1 (Hsp70.1) affects neuronal cell fate by regulating lysosomal acid sphingomyelinase. J Biol Chem (2014) 289:27432-43. doi:10.1074/jbc.M114.560334
218. Werneburg NW, Guicciardi ME, Bronk SF, Gores GJ. Tumor necrosis factor-alpha-associated lysosomal permeabilization is cathepsin B dependent. Am J Physiol Gastrointest Liver Physiol (2002) 283:G947-56. doi:10.1152/ajpgi.00151.2002
219. Shao C, Roberts KN, Markesbery WR, Scheff SW, Lovell MA. Oxidative stress in head trauma in aging. Free Radic Biol Med (2006) 41:77-85. doi:10.1016/j.freeradbiomed.2006.03.007
220. Bayir H, Kagan VE, Borisenko GG, Tyurina YY, Janesko KL, Vagni VA, et al. Enhanced oxidative stress in iNOS-deficient mice after traumatic brain injury: support for a neuroprotective role of iNOS. J Cereb Blood Flow Metab (2005) 25:673-84. doi:10.1038/sj.jcbfm.9600068
221. Kurz T, Terman A, Gustafsson B, Brunk UT. Lysosomes in iron metabolism, ageing and apoptosis. Histochem Cell Biol (2008) 129:389-406. doi:10.1007/s00418-008-0394-y
222. Boya P, Kroemer G. Lysosomal membrane permeabilization in cell death. Oncogene (2008) 27:6434-51. doi:10.1038/onc.2008.310
223. Tontchev AB, Yamashima T. Ischemic delayed neuronal death: role of the cysteine proteases calpain and cathepsins. Neuropathology (1999) 19:356-65. doi:10.1046/j.1440-1789.1999.00259.x
224. Guicciardi ME, Leist M, Gores GJ. Lysosomes in cell death. Oncogene (2004) 23:2881-90. doi:10.1038/sj.onc.1207512
225. Lima H Jr, Jacobson LS, Goldberg MF, Chandran K, Diaz-Griffero F, Lisanti MP, et al. Role of lysosome rupture in controlling Nlrp3 signaling and necrotic cell death. Cell Cycle (2013) 12:1868-78. doi:10.4161/cc.24903
226. Wei MC, Lindsten T, Mootha VK, Weiler S, Gross A, Ashiya M, et al. tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. Genes Dev (2000) 14:2060-71.
227. Michallet MC, Saltel F, Preville X, Flacher M, Revillard JP, Genestier L. Cathepsin-B-dependent apoptosis triggered by antithymocyte globulins: a novel mechanism of T-cell depletion. Blood (2003) 102:3719-26. doi:10.1182/blood-2003-04-1075
228. Kingham PJ, Pocock JM. Microglial secreted cathepsin B induces neuronal apoptosis. J Neurochem (2001) 76:1475-84. doi:10.1046/j.1471-4159.2001.00146.x
229. Hornung V, Bauernfeind F, Halle A, Samstad EO, Kono H, Rock KL, et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol (2008) 9:847-56. doi:10.1038/ni.1631
230. Schotte P, Van Criekinge W, Van De Craen M, Van Loo G, Desmedt M, Grooten J, et al. Cathepsin B-mediated activation of the proinflammatory caspase-11. Biochem Biophys Res Commun (1998) 251:379-87. doi:10.1006/bbrc.1998.9425
231. Kang SJ, Wang S, Hara H, Peterson EP, Namura S, Amin-Hanjani S, et al. Dual role of caspase-11 in mediating activation of caspase-1 and caspase-3 under pathological conditions. J Cell Biol (2000) 149:613-22. doi:10.1083/jcb.149.3.613
232. Stahel PF, Smith WR, Bruchis J, Rabb CH. Peroxisome proliferator-activated receptors: "key" regulators of neuroinflammation after traumatic brain injury. PPAR Res (2008) 2008:538141. doi:10.1155/2008/538141
233. Besson VC, Chen XR, Plotkine M, Marchand-Verrecchia C. Fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, exerts neuroprotective effects in traumatic brain injury. Neurosci Lett (2005) 388:7-12. doi:10.1016/j.neulet.2005.06.019
234. Chen XR, Besson VC, Palmier B, Garcia Y, Plotkine M, Marchand-Leroux C. Neurological recovery-promoting, anti-inflammatory, and anti-oxidative effects afforded by fenofibrate, a PPAR alpha agonist, in traumatic brain injury. J Neurotrauma (2007) 24:1119-31. doi:10.1089/neu.2006.0216
235. Reichenbach G, Starzinski-Powitz A, Doll M, Hrgovic I, Valesky EM, Kippenberger S, et al. Ligand activation of peroxisome proliferator-activated receptor delta suppresses cathepsin B expression in human endothelial cells in a posttranslational manner. Exp Dermatol (2012) 21:751-7. doi:10.1111/exd.12002
236. Medana IM, Esiri MM. Axonal damage: a key predictor of outcome in human CNS diseases. Brain (2003) 126:515-30. doi:10.1093/brain/awg061
237. Calabrese B, Halpain S. Essential role for the PKC target MARCKS in maintaining dendritic spine morphology. Neuron (2005) 48:77-90. doi:10.1016/j.neuron.2005.08.027
238. Lai Y, Hickey RW, Chen Y, Bayir H, Sullivan ML, Chu CT, et al. Autophagy is increased after traumatic brain injury in mice and is partially inhibited by the antioxidant gamma-glutamylcysteinyl ethyl ester. J Cereb Blood Flow Metab (2008) 28:540-50. doi:10.1038/sj.jcbfm.9600551
239. Zhang YB, Li SX, Chen XP, Yang L, Zhang YG, Liu R, et al. Autophagy is activated and might protect neurons from degeneration after traumatic brain injury. Neurosci Bull (2008) 24:143-9. doi:10.1007/s12264-008-1108-0
240. Wang YQ, Wang L, Zhang MY, Wang T, Bao HJ, Liu WL, et al. Necrostatin-1 suppresses autophagy and apoptosis in mice traumatic brain injury model. Neurochem Res (2012) 37:1849-58. doi:10.1007/s11064-012-0791-4
241. Luo CL, Li BX, Li QQ, Chen XP, Sun YX, Bao HJ, et al. Autophagy is involved in traumatic brain injury-induced cell death and contributes to functional outcome deficits in mice. Neuroscience (2011) 184:54-63. doi:10.1016/j.neuroscience.2011.03.021
242. Kadowaki M, Karim MR. Cytosolic LC3 ratio as a quantitative index of macroautophagy. Methods Enzymol (2009) 452:199-213. doi:10.1016/S0076-6879(08)03613-6
243. Kang R, Zeh HJ, Lotze MT, Tang D. The beclin 1 network regulates autophagy and apoptosis. Cell Death Differ (2011) 18:571-80. doi:10.1038/cdd.2010.191
244. Bjorkoy G, Lamark T, Pankiv S, Overvatn A, Brech A, Johansen T. Monitoring autophagic degradation of p62/SQSTM1. Methods Enzymol (2009) 452:181-97. doi:10.1016/S0076-6879(08)03612-4
245. Wu YT, Tan HL, Shui G, Bauvy C, Huang Q, Wenk MR, et al. Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. J Biol Chem (2010) 285:10850-61. doi:10.1074/jbc.M109.080796
246. Klionsky DJ, Abeliovich H, Agostinis P, Agrawal DK, Aliev G, Askew DS, et al. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy (2008) 4:151-75. doi:10.4161/auto.5338
247. Knoblach SM, Alroy DA, Nikolaeva M, Cernak I, Stoica BA, Faden AI. Caspase inhibitor z-DEVD-fmk attenuates calpain and necrotic cell death in vitro and after traumatic brain injury. J Cereb Blood Flow Metab (2004) 24:1119-32. doi:10.1097/01.WCB.0000138664.17682.32
248. Xu J, Wang H, Ding K, Lu X, Li T, Wang J, et al. Inhibition of cathepsin S produces neuroprotective effects after traumatic brain injury in mice. Mediators Inflamm (2013) 2013:187873. doi:10.1155/2013/187873
249. Ray SK, Matzelle DC, Wilford GG, Hogan EL, Banik NL. E-64-d prevents both calpain upregulation and apoptosis in the lesion and penumbra following spinal cord injury in rats. Brain Res (2000) 867:80-9. doi:10.1016/S0006-8993(00)02260-5
250. Inuzuka T, Tamura A, Sato S, Kirino T, Toyoshima I, Miyatake T. Suppressive effect of E-64c on ischemic degradation of cerebral proteins following occlusion of the middle cerebral artery in rats. Brain Res (1990) 526:177-9. doi:10.1016/0006-8993(90)90269-H
251. Seyfried DM, Veyna R, Han Y, Li K, Tang N, Betts RL, et al. A selective cysteine protease inhibitor is non-toxic and cerebroprotective in rats undergoing transient middle cerebral artery ischemia. Brain Res (2001) 901:94-101. doi:10.1016/S0006-8993(01)02289-2
252. Yoshida M, Yamashima T, Zhao L, Tsuchiya K, Kohda Y, Tonchev AB, et al. Primate neurons show different vulnerability to transient ischemia and response to cathepsin inhibition. Acta Neuropathol (2002) 104:267-72.
253. Yang D, Han Y, Zhang J, Ding C, Anagli J, Seyfried DM. Improvement in recovery after experimental intracerebral hemorrhage using a selective cathepsin B and L inhibitor. J Neurosurg (2011) 114:1110-6. doi:10.3171/2010.6.JNS091856
254. Lyo V, Cattaruzza F, Kim TN, Walker AW, Paulick M, Cox D, et al. Active cathepsins B, L, and S in murine and human pancreatitis. Am J Physiol Gastrointest Liver Physiol (2012) 303:G894-903. doi:10.1152/ajpgi.00073.2012
255. Trinchese F, Fa M, Liu S, Zhang H, Hidalgo A, Schmidt SD, et al. Inhibition of calpains improves memory and synaptic transmission in a mouse model of Alzheimer disease. J Clin Invest (2008) 118:2796-807. doi:10.1172/JCI34254
256. Hook G, Hook V, Kindy M. The cysteine protease inhibitor, E64d, reduces brain amyloid-beta and improves memory deficits in Alzheimer's disease animal models by inhibiting cathepsin B, but not BACE1, beta-secretase activity. J Alzheimers Dis (2011) 26:387-408. doi:10.3233/JAD-2011-110101
257. Hanada K, Tamai M, Yamagishi S, Ohmura J, Sawada I, Tanaka H. Isolation and characterization of E-64, a new thiol protease inhibitor. Agric Biol Chem (1978) 42:523-8. doi:10.1271/bbb1961.42.523
258. Parkes C, Kembhavi AA, Barrett AJ. Calpain inhibition by peptide epoxides. Biochem J (1985) 230:509-16.
259. Sasaki T, Kikuchi T, Fukui I, Murachi T. Inactivation of calpain I and calpain II by specificity-oriented tripeptidyl chloromethyl ketones. J Biochem (1986) 99:173-9.
260. Susa M, Luong-Nguyen NH, Cappellen D, Zamurovic N, Gamse R. Human primary osteoclasts: in vitro generation and applications as pharmacological and clinical assay. J Transl Med (2004) 2:6. doi:10.1186/1479-5876-2-6
261. Hashida S, Towatari T, Kominami E, Katunuma N. Inhibitions by E-64 derivatives of rat liver cathepsin B and cathepsin L in vitro and in vivo. J Biochem (1980) 88:1805-11.
262. Tamai M, Matsumoto K, Omura S, Koyama I, Ozawa Y, Hanada K. In vitro and in vivo inhibition of cysteine proteinases by EST, a new analog of E-64. J Pharmacobiodyn (1986) 9:672-7. doi:10.1248/bpb1978.9.672
263. Tamai M, Hanada K, Adachi T, Oguma K, Kashiwagi K, Omura S, et al. Papain inhibitions by optically active E-64 analogs. J Biochem (1981) 90:255-7.
264. Murata M, Miyashita S, Yokoo C, Tamai M, Hanada K, Hatayama K, et al. Novel epoxysuccinyl peptides. Selective inhibitors of cathepsin B, in vitro. FEBS Lett (1991) 280:307-10. doi:10.1016/0014-5793(91)80318-W
265. Towatari T, Nikawa T, Murata M, Yokoo C, Tamai M, Hanada K, et al. Novel epoxysuccinyl peptides. A selective inhibitor of cathepsin B, in vivo. FEBS Lett (1991) 280:311-5. doi:10.1016/0014-5793(91)80319-X
266. Katunuma N. Structure-based development of specific inhibitors for individual cathepsins and their medical applications. Proc Jpn Acad Ser B Phys Biol Sci (2011) 87:29-39. doi:10.2183/pjab.87.29
267. Montaser M, Lalmanach G, Mach L. CA-074, but not its methyl ester CA-074Me, is a selective inhibitor of cathepsin B within living cells. Biol Chem (2002) 383:1305-8. doi:10.1515/BC.2002.147
268. Bogyo M, Verhelst S, Bellingard-Dubouchaud V, Toba S, Greenbaum D. Selective targeting of lysosomal cysteine proteases with radiolabeled electrophilic substrate analogs. Chem Biol (2000) 7:27-38. doi:10.1016/S1074-5521(00)00061-2
269. Buttle DJ, Murata M, Knight CG, Barrett AJ. CA074 methyl ester: a proinhibitor for intracellular cathepsin B. Arch Biochem Biophys (1992) 299:377-80. doi:10.1016/0003-9861(92)90290-D
270. Rozman-Pungercar J, Kopitar-Jerala N, Bogyo M, Turk D, Vasiljeva O, Stefe I, et al. Inhibition of papain-like cysteine proteases and legumain by caspase-specific inhibitors: when reaction mechanism is more important than specificity. Cell Death Differ (2003) 10:881-8. doi:10.1038/sj.cdd.4401247
271. Schotte P, Declercq W, Van Huffel S, Vandenabeele P, Beyaert R. Non-specific effects of methyl ketone peptide inhibitors of caspases. FEBS Lett (1999) 442:117-21. doi:10.1016/S0014-5793(98)01640-8
272. Vancompernolle K, Van Herreweghe F, Pynaert G, Van De Craen M, De Vos K, Totty N, et al. Atractyloside-induced release of cathepsin B, a protease with caspase-processing activity. FEBS Lett (1998) 438:150-8. doi:10.1016/S0014-5793(98)01275-7
273. Jacobsen W, Christians U, Benet LZ. In vitro evaluation of the disposition of a novel cysteine protease inhibitor. Drug Metab Dispos (2000) 28:1343-51.
274. Boutte A, Deng-Bryant Y, Johnson D, Tortella FC, Dave J, Shear DA, et al. Serum GFAP predicts tissue GFAP break down products and therapeutic efficacy after penetrating ballistic-like brain injury. J Neurotrauma (2015). doi:10.1089/neu.2014.3672
275. Kochanek PM, Bramlett H, Dietrich WD, Dixon CE, Hayes RL, Povlishock J, et al. A novel multicenter preclinical drug screening and biomarker consortium for experimental traumatic brain injury: operation brain trauma therapy. J Trauma (2011) 71:S15-24. doi:10.1097/TA.0b013e31822117fe
276. Deng Y, Thompson BM, Gao X, Hall ED. Temporal relationship of peroxynitrite-induced oxidative damage, calpain-mediated cytoskeletal degradation and neurodegeneration after traumatic brain injury. Exp Neurol (2007) 205:154-65. doi:10.1016/j.expneurol.2007.01.023
277. Yamada KH, Kozlowski DA, Seidl SE, Lance S, Wieschhaus AJ, Sundivakkam P, et al. Targeted gene inactivation of calpain-1 suppresses cortical degeneration due to traumatic brain injury and neuronal apoptosis induced by oxidative stress. J Biol Chem (2012) 287:13182-93. doi:10.1074/jbc.M111.302612
278. Wang X, Jung J, Asahi M, Chwang W, Russo L, Moskowitz MA, et al. Effects of matrix metalloproteinase-9 gene knock-out on morphological and motor outcomes after traumatic brain injury. J Neurosci (2000) 20:7037-42.
279. Yanamandra N, Gumidyala KV, Waldron KG, Gujrati M, Olivero WC, Dinh DH, et al. Blockade of cathepsin B expression in human glioblastoma cells is associated with suppression of angiogenesis. Oncogene (2004) 23:2224-30. doi:10.1038/sj.onc.1207338
280. Tsubokawa T, Solaroglu I, Yatsushige H, Cahill J, Yata K, Zhang JH. Cathepsin and calpain inhibitor E64d attenuates matrix metalloproteinase-9 activity after focal cerebral ischemia in rats. Stroke (2006) 37:1888-94. doi:10.1161/01.STR.0000227259.15506.24
281. Schiefer IT, Tapadar S, Litosh V, Siklos M, Scism R, Wijewickrama GT, et al. Design, synthesis, and optimization of novel epoxide incorporating peptidomimetics as selective calpain inhibitors. J Med Chem (2013) 56:6054-68. doi:10.1021/jm4006719
282. Tamai M, Omura S, Kimura M, Hanada K, Sugita H. Prolongation of life span of dystrophic hamster by cysteine proteinase inhibitor, loxistation (EST). J Pharmacobiodyn (1987) 10:678-81. doi:10.1248/bpb1978.10.678
283. Satoyoshi E. Therapeutic trials on progressive muscular dystrophy. Intern Med (1992) 31:841-6. doi:10.2169/internalmedicine.31.841
284. Watanabe T, Fukushima K, Ushiyama Y, Noda K, Suwa T. Pharmacokinetics of EST (report 5): pharmacokinetics of EST ih humans. Kiso Rinsho (1986) 20:362-6.
285. Barrett AJ, Kembhavi AA, Brown MA, Kirschke H, Knight CG, Tamai M, et al. L-trans-Epoxysuccinyl-leucylamido(4-guanidino)butane (E-64) and its analogues as inhibitors of cysteine proteinases including cathepsins B, H and L. Biochem J (1982) 201:189-98.
286. Suzuki K. Reaction of calcium-activated neutral protease (CANP) with an epoxysuccinyl derivative (E64c) and iodoacetic acid. J Biochem (1983) 93:1305-12.
287. Cravatt BF, Wright AT, Kozarich JW. Activity-based protein profiling: from enzyme chemistry to proteomic chemistry. Annu Rev Biochem (2008) 77:383-414. doi:10.1146/annurev.biochem.75.101304.124125
288. Niphakis MJ, Cravatt BF. Enzyme inhibitor discovery by activity-based protein profiling. Annu Rev Biochem (2014) 83:341-77. doi:10.1146/annurev-biochem-060713-035708
289. Sanman LE, Bogyo M. Activity-based profiling of proteases. Annu Rev Biochem (2014) 83:249-73. doi:10.1146/annurev-biochem-060713-035352
290. Blum G, Von Degenfeld G, Merchant MJ, Blau HM, Bogyo M. Noninvasive optical imaging of cysteine protease activity using fluorescently quenched activity-based probes. Nat Chem Biol (2007) 3:668-77. doi:10.1038/nchembio.2007.26
291. Boutte AM, Friedman DB, Bogyo M, Min Y, Yang L, Lin PC. Identification of a myeloid-derived suppressor cell cystatin-like protein that inhibits metastasis. FASEB J (2011) 25:2626-37. doi:10.1096/fj.10-180604
292. Fukushima K, Yoshida H, Osabe W, Shinozaki F, Kudo K, Arai M, et al. Pharmacokinetics of EST (report 1): absorption and excretion of 14C-EST. Kiso Rinsho (1986) 20:319-27.
293. Fukushima K, Kono Y, Osabe W, Shinozaki F, Kudo K, Arai M, et al. Pharmacokinetics of EST (report 2): tissue distribution of 14C-EST. Kiso Rinsho (1986) 20:328-41.
294. Ishiura S, Hanada K, Tamai M, Kashiwagi K, Sugita H. The effect of an in vivo-injected thiol protease inhibitor, E-64-c, on the calcium-induced degeneration of myofilaments. J Biochem (1981) 90:1557-60.
295. Miyahara T, Shimojo S, Toyohara K, Imai T, Miyajima M, Honda H, et al. Clinical phase I trial of thiol protease inhibitor (Report 2): safety and pharmacokinetics in continuous administration. Rinsho Yakuri (1985) 16:537-46. doi:10.3999/jscpt.16.357
296. Miyahara T, Shimojo S, Toyohara K, Imai T, Miyajima M, Honda H, et al. Phase I clinical trial of thiol protease inhibitor EST (report 1): safety and pharmacokinetics with single administration. Rinsho Yakuri (1985) 16:357-65. doi:10.3999/jscpt.16.357
297. Fukushima K, Arai M, Tamai M, Yokoo C, Murata M, Suwa T, et al. Metabolic fate of loxistatin in rat. Xenobiotica (1990) 20:1043-51. doi:10.3109/00498259009046825
298. Yasui H, Goto H, Suzuki H, Sakai S, Takamura T, Nakane S. Toxicological studies on ethyl( + )-(2S,2S)-3[(S)-3-methyl-1-(3-methylbutylcarbamoyl)butylcarbamoyl]-2-oxiranecarboxylate (EST)(report IX) mutagenicity study. Iyakuhin Kenkyu (1986) 17:815-25.
299. Setoyama K, Koike M, Abe S, Tsutsui Y, Tarumoto Y, Nakane S. Toxicological studies of ethyl (+)-(2S,3S)-3-[(S)-3-methyl-1-(3-methylbutylcarbamoyl)butylcarbamoyl]-2-oxiranecarboxylate (EST) (report 1): acute toxicity studies of EST and metabolite and by-product of EST. Iyakuhin Kenkyu (1986) 17:736-43.
300. Tarumoto Y, Sakagawa T, Tsutsui Y, Kawanishi M, Kimura M, Nakane S. Toxicological studies on ethyl(+)-(2S,2S)-3[(S)-3-methyl-1-(3-methylbutylcarbamoyl)butylcarbamoyl]-2-oxiranecarboxylate (EST)(report V) subacute toxicity in dogs. Iyakuhin Kenkyu (1986) 17:768-80.
301. Kimura M, Yagi K, Fujinuma S, Tsuchida T, Tarumoto Y, Noda K, et al. Toxicological studies on ethyl(+)-(2S,2S)-3[(S)-3-methyl-1-(3-methylbutylcarbamoyl)butylcarbamoyl]-2-oxiranecarboxylate (EST) (report III) subacute toxicity in rats. Iyakuhin Kenkyu (1986) 17:744-67.
302. Tarumoto Y, Sakagawa T, Tsutsui Y, Kawanishi M, Watanabe T, Nakane S. Toxicological studies on ethyl(+)-(2S,2S)-3[(S)-3-methyl-1-(3-methylbutylcarbamoyl)butylcarbamoyl]-2-oxiranecarboxylate (EST)(report VII) chronic toxicity study in dogs. Iyakuhin Kenkyu (1986) 17:802-14.
303. Ohshima T, Watanabe T, Nagato C, Kimura M, Tsuchida T, Nakane S. Toxicological studies on ethyl(+)-(2S,2S)-3[(S)-3-methyl-1-(3-methylbutylcarbamoyl)butylcarbamoyl]-2-oxiranecarboxylate (EST)(report VI) Chronic toxicity study in rats. Iyakuhin Kenkyu (1986) 17:781-801.
304. Fukushima K, Arai M, Kohno Y, Suwa T, Satoh T. An epoxysuccinic acid derivative(loxistatin)-induced hepatic injury in rats and hamsters. Toxicol Appl Pharmacol (1990) 105:1-12. doi:10.1016/0041-008X(90)90353-V
305. Yamada T, Nishiyama T, Ohno H, Nakane S. Reproduction studies of ethyl(+)-(2S,2S)-3[(S)-3-methyl-1-(3-methylbutylcarbamoyl)butylcarbamoyl]-2-oxiranecarboxylate (EST) (report III): study of administration to rabbits during organogenesis. Iyakuhin Kenkyu (1986) 17:632-8.
306. Yamada T, Uchida H, Inoue T, Ohba Y, Nakane S. Reproduction studies of ethyl(+)-(2S,2S)-3[(S)-3-methyl-1-(3-methylbutylcarbamoyl)butylcarbamoyl]-2-oxiranecarboxylate (EST) (report II): study of administration to rats during organogenesis. Iyakuhin Kenkyu (1986) 14:617-31.
307. Yamada T, Nishiyama T, Nakane S. Reproduction studies of ethyl(+)-(2S,2S)-3[(S)-3-methyl-1-(3-methylbutylcarbamoyl)butylcarbamoyl]-2-oxiranecarboxylate (EST) (report I): study of administration to rats prior to and in early stage of gestation. Iyakuhin Kenkyu (1986) 17:609-16.
308. Yamada T, Uchida H, Ohno H, Matsuzawa N, Nakane S. Reproduction studies of ethyl(+)-(2S,2S)-3[(S)-3-methyl-1-(3-methylbutylcarbamoyl)butylcarbamoyl]-2-oxiranecarboxylate (EST) (report IV): study of administration to rats during perinatal and postnatal periods. Iyakuhin Kenkyu (1986) 17:639-51.
309. Huryn DM, Smith AB III. The identification, characterization and optimization of small molecule probes of cysteine proteases: experiences of the Penn Center for Molecular Discovery with cathepsin B and cathepsin L. Curr Top Med Chem (2009) 9:1206-16. doi:10.2174/156802609789753653