Specific calpain inhibition by calpastatin prevents tauopathy and neurodegeneration and restores normal lifespan in tau P301L Mice

Journal of Neuroscience

Volumn 34, Issue 28, 2014, Pages 9222-9234

  Rao, Mala V ^a,b   McBrayer, Mary Kate ^a   Campbell, Jabbar ^a   Kumar, Asok ^a   Hashim, Audrey ^a   Sershen, Henry ^a   Stavrides, Philip H ^a   Ohno, Masuo ^a,b   Hutton, Michael ^d   Nixon, Ralph A ^a,b,c  

^a NATHAN S KLINE INSTITUTE FOR PSYCHIATRIC RESEARCH   (United States)

^b NEW YORK UNIVERSITY MEDICAL CENTER   (United States)

^c NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d ELI LILLY AND COMPANY   (United States)

Author keywords

Ambulatory movements; Calcium; Fractionation; Insoluble extracts; Nesting behavior

Indexed keywords

CALPAIN; CALPASTATIN; CYCLIN DEPENDENT KINASE 5; CYTOSKELETON PROTEIN; TAU PROTEIN; TISSUE EXTRACT;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVATION; FEMALE; GENE OVEREXPRESSION; IMMUNOCOMPETENT CELL; IMMUNOCYTOCHEMISTRY; LIFESPAN; LOCOMOTION; MALE; MORPHOMETRICS; MOUSE; NERVE DEGENERATION; NESTING; NEUROFIBRILLARY TANGLE; NONHUMAN; OLIGOMERIZATION; PHOSPHORYLATION; POLYACRYLAMIDE GEL ELECTROPHORESIS; PRIORITY JOURNAL; PROTEIN DEGRADATION; SPATIAL MEMORY; TAUOPATHY; WESTERN BLOTTING; WORKING MEMORY; Y-MAZE TEST;

AMBULATORY MOVEMENTS; CALCIUM; FRACTIONATION; INSOLUBLE EXTRACTS; NESTING BEHAVIOR;

ANIMALS; BEHAVIOR, ANIMAL; CALCIUM-BINDING PROTEINS; CALPAIN; CYSTEINE PROTEINASE INHIBITORS; FEMALE; LONGEVITY; MALE; MICE; MICE, TRANSGENIC; NERVE DEGENERATION; SURVIVAL RATE; TAU PROTEINS; TAUOPATHIES; TREATMENT OUTCOME;

EID: 84903975926     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.1132-14.2014     Document Type: Article

References (112)

1. Adamec E., Mohan P, Vonsattel JP, Nixon RA (2002) Calpain activation in neurodegenerative diseases: confocal immunofluorescence study with antibodies specifically recognizing the active form of calpain 2. Acta Neuropathol 104:92-104. CrossRef Medline
2. Ahlijanian M. K, Barrezueta NX, Williams RD, Jakowski A, Kowsz KP, McCarthy S, Coskran T, Carlo A, Seymour PA, Burkhardt JE, Nelson RB, Mc-Neish J. D (2000) Hyperphosphorylated tau and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5. Proc Natl Acad Sci U S A 97:2910-2915. CrossRef Medline
3. Anagli J., Han Y, Stewart L, Yang D, Movsisyan A, Abounit K, Seyfried D (2009) A novel calpastatin-based inhibitor improves postischemic neurological recovery. Biochem Biophys Res Commun 385:94-99. CrossRef Medline
4. Arendash G. W, Lewis J, Leighty RE, McGowan E, Cracchiolo JR, Hutton M, Garcia M. F (2004) Multi-metric behavioral comparison of APPsw and P301L models for Alzheimer's disease: linkage of poorer cognitive performance to tau pathology in forebrain. Brain Res 1012:29-41. CrossRef Medline
5. Augustinack J. C, Sanders JL, Tsai LH, Hyman BT (2002) Colocalization and fluorescence resonance energy transfer between cdk5 and AT8 suggests a close association in pre-neurofibrillary tangles and neurofibrillary tangles. J Neuropathol Exp Neurol 61:557-564. Medline
6. Bartus R. (1997) The calpain hypothesis of neurodegeneration: evidence for a common cytotoxic pathway. Neuroscientist 3:314-327.
7. Bartus R. T, Elliott PJ, Hayward NJ, Dean RL, Harbeson S, Straub JA, Li Z, Powers J. C (1995) Calpain as a novel target for treating acute neurodegenerative disorders. Neurol Res 17:249-258. Medline
8. Berger Z., Roder H, Hanna A, Carlson A, Rangachari V, Yue M, Wszolek Z, Ashe K., Knight J, Dickson D, Andorfer C, Rosenberry TL, Lewis J, Hutton M, Janus C (2007) Accumulation of pathological tau species and memory loss in a conditional model of tauopathy. J Neurosci 27:3650-3662. CrossRef Medline
9. Binder L. I, Guillozet-Bongaarts AL, Garcia-Sierra F, Berry RW (2005) Tau, tangles, and Alzheimer's disease. Biochim Biophys Acta 1739:216-223. CrossRef Medline
10. Boillée S., Yamanaka K, Lobsiger CS, Copeland NG, Jenkins NA, Kassiotis G, Kollias G., Cleveland DW (2006) Onset and progression in inherited ALS determined by motor neurons and microglia. Science 312:1389-1392. CrossRef Medline
11. Castillo-Carranza D. L, Gerson JE, Sengupta U, Guerrero-Muñoz MJ, Lasagna-Reeves C. A, Kayed R (2014a) Specific targeting of tau oligomers in hTau mice prevents cognitive impairment and tau toxicity following injection with brain-derived tau oligomeric seeds. J Alzheimers Dis 40: S97-S111. CrossRef Medline
12. Castillo-Carranza D. L, Sengupta U, Guerrero-Muñoz MJ, Lasagna-Reeves CA, Gerson JE, Singh G, Estes DM, Barrett AD, Dineley KT, Jackson GR, Kayed R. (2014b) Passive immunization with Tau oligomer monoclonal antibody reverses tauopathy phenotypes without affecting hyperphosphorylated neurofibrillary tangles. J Neurosci 34:4260-4272. CrossRef Medline
13. Cheung Z. H, Ip NY (2012) Cdk5: a multifaceted kinase in neurodegenerative diseases. Trends Cell Biol 22:169-175. CrossRef Medline
14. Congdon E. E, Wu JW, Myeku N, Figueroa YH, Herman M, Marinec PS, Gestwicki J. E, Dickey CA, Yu WH, Duff KE (2012) Methylthioninium chloride (methylene blue) induces autophagy and attenuates tauopathy in vitro and in vivo. Autophagy 8:609-622. CrossRef Medline
15. de Calignon A., Fox LM, Pitstick R, Carlson GA, Bacskai BJ, Spires-Jones TL, Hyman B. T (2010) Caspase activation precedes and leads to tangles. Nature 464:1201-1204. CrossRef Medline
16. de Calignon A., Polydoro M, Suárez-Calvet M, William C, Adamowicz DH, Kopeikina K. J, Pitstick R, Sahara N, Ashe KH, Carlson GA, Spires-Jones TL, Hyman BT (2012) Propagation of tau pathology in a model of early Alzheimer's disease. Neuron 73:685-697. CrossRef Medline
17. Dolan P. J, Johnson GV (2010) A caspase cleaved form of tau is preferentially degraded through the autophagy pathway. J Biol Chem 285:21978-21987. CrossRef Medline
18. Evans C. G, Jinwal UK, Makley LN, Dickey CA, Gestwicki JE (2011) Identification of dihydropyridines that reduce cellular tau levels. Chem Commun (Camb) 47:529-531. CrossRef
19. Ferreira A., Bigio EH (2011) Calpain-mediated tau cleavage: a mechanism leading to neurodegeneration shared by multiple tauopathies. Mol Med 17:676-685. CrossRef Medline
20. Fox L. M, William CM, Adamowicz DH, Pitstick R, Carlson GA, Spires-Jones TL, Hyman BT (2011) Soluble tau species, not neurofibrillary aggregates, disrupt neural system integration in a tau transgenic model. J Neuropathol Exp Neurol 70:588-595. CrossRef Medline
21. Furukawa K., D'Souza I, Crudder CH, Onodera H, Itoyama Y, Poorkaj P, Bird TD, Schellenberg GD (2000) Pro-apoptotic effects of tau mutations in chromosome 17 frontotemporal dementia and parkinsonism. Neuroreport 11:57-60. CrossRef Medline
22. Furukawa K., Wang Y, Yao PJ, Fu W, Mattson MP, Itoyama Y, Onodera H, D'Souza I., Poorkaj PH, Bird TD, Schellenberg GD (2003) Alteration in calcium channel properties is responsible for the neurotoxic action of a familial frontotemporal dementia tau mutation. J Neurochem 87:427-436. CrossRef Medline
23. Gamblin T. C, Chen F, Zambrano A, Abraha A, Lagalwar S, Guillozet AL, Lu M, Fu Y, Garcia-Sierra F, LaPointe N, Miller R, Berry RW, Binder LI, Cryns V. L (2003) Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer's disease. Proc Natl Acad Sci U S A 100: 10032-10037. CrossRef Medline
24. García-Sierra F., Jarero-Basulto JJ, Kristofikova Z, Majer E, Binder LI, Ripova D (2012) Ubiquitin is associated with early truncation of tau protein at aspartic acid(421) during the maturation of neurofibrillary tangles in Alzheimer's disease. Brain Pathol 22:240-250. CrossRef Medline
25. Garg S., Timm T, Mandelkow EM, Mandelkow E, Wang Y (2011) Cleavage of Tau by calpain in Alzheimer's disease: the quest for the toxic 17 kD fragment. Neurobiol Aging 32:1-14. CrossRef Medline
26. Grynspan F., Griffin WR, Cataldo A, Katayama S, Nixon RA (1997) Active site-directed antibodies identify calpain II as an early-appearing and pervasive component of neurofibrillary pathology in Alzheimer's disease. Brain Res 763:145-158. CrossRef Medline
27. Gundersen H. J (1988) The nucleator. J Microsc 151:3-21. CrossRef Medline
28. Hashiguchi M., Saito T, Hisanaga S, Hashiguchi T (2002) Truncation of CDK5 activator p35 induces intensive phosphorylation of Ser202/Thr205 of human tau. J Biol Chem 277:44525-44530. CrossRef Medline
29. Henkins K. M, Sokolow S, Miller CA, Vinters HV, Poon WW, Cornwell LB, Saing T., Gylys KH (2012) Extensive p-tau pathology and SDS-stable p-tau oligomers in Alzheimer's cortical synapses. Brain Pathol 22:826-833. CrossRef Medline
30. Higuchi M., Tomioka M, Takano J, Shirotani K, Iwata N, Masumoto H, Maki M, Itohara S, Saido TC (2005) Distinct mechanistic roles of calpain and caspase activation in neurodegeneration as revealed in mice overexpressing their specific inhibitors. J Biol Chem 280:15229-15237. CrossRef Medline
31. Higuchi M., Iwata N, Matsuba Y, Takano J, Suemoto T, Maeda J, Ji B, Ono M, Staufenbiel M., Suhara T, Saido TC (2012) Mechanistic involvement of the calpain-calpastatin system in Alzheimer neuropathology. FASEB J 26:1204-1217. CrossRef Medline
32. Horowitz P. M, Patterson KR, Guillozet-Bongaarts AL, Reynolds MR, Carroll CA, Weintraub ST, Bennett DA, Cryns VL, Berry RW, Binder LI (2004) Early N-terminal changes and caspase-6 cleavage of tau in Alzheimer's disease. J Neurosci 24:7895-7902. CrossRef Medline
33. Hosokawa M., Arai T, Masuda-Suzukake M, Nonaka T, Yamashita M, Akiyama H., HasegawaM (2012) Methylene blue reduced abnormal tau accumulation in P301L tau transgenic mice. PLoS One 7:e52389. CrossRef Medline
34. Hutton M., Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S., Chakraverty S, Isaacs A, Grover A, Hackett J, Adamson J, Lincoln S, Dickson D, Davies P, Petersen RC, Stevens M, de Graaff E, Wauters E, van Baren J, et al. (1998) Association of missense and 5-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393:702-705. CrossRef Medline
35. Ihara Y., Morishima-Kawashima M, Nixon R (2012) The ubiquitinproteasome system and the autophagic-lysosmal system in Alzheimer disease. Cold Spring Harb Perspect Med 2:a006361. Medline
36. Iqbal K., Liu F, Gong CX, Grundke-Iqbal I (2010) Tau in Alzheimer disease and related tauopathies. Curr Alzheimer Res 7:656-664. CrossRef Medline
37. Johnson G. V (2006) Tau phosphorylation and proteolysis: insights and perspectives. J Alzheimers Dis 9[3 Suppl]:243-250. Medline
38. Khurana V., Elson-Schwab I, Fulga TA, Sharp KA, Loewen CA, Mulkearns E, Tyynelä J., Scherzer CR, Feany MB (2010) Lysosomal dysfunction promotes cleavage and neurotoxicity of tau in vivo. PLoS Genet 6:e1001026. CrossRef Medline
39. Kickstein E., Krauss S, Thornhill P, Rutschow D, Zeller R, Sharkey J, Williamson R, Fuchs M, Köhler A, Glossmann H, Schneider R, Sutherland C, Schweiger S. (2010) Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling. Proc Natl Acad Sci U S A 107:21830-21835. CrossRef Medline
40. LaFerla F. M (2002) Calcium dyshomeostasis and intracellular signalling in Alzheimer's disease. Nat Rev Neurosci 3:862-872. CrossRef Medline
41. Lasagna-Reeves C. A, Castillo-Carranza DL, Guerrero-Muoz MJ, Jackson GR, Kayed R. (2010) Preparation and characterization of neurotoxic tau oligomers. Biochemistry 49:10039-10041. CrossRef Medline
42. Lasagna-Reeves C. A, Castillo-Carranza DL, Jackson GR, Kayed R (2011a) Tau oligomers as potential targets for immunotherapy for Alzheimer's disease and tauopathies. Curr Alzheimer Res 8:659-665. CrossRef Medline
43. Lasagna-Reeves C. A, Castillo-Carranza DL, Sengupta U, Clos AL, Jackson GR, Kayed R. (2011b) Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice. Mol Neurodegener 6:39. CrossRef Medline
44. Lasagna-Reeves C. A, Castillo-Carranza DL, Sengupta U, Guerrero-Munoz MJ, Kiritoshi T, Neugebauer V, Jackson GR, Kayed R (2012) Alzheimer brain-derived tau oligomers propagate pathology from endogenous tau. Sci Rep 2:700. CrossRef Medline
45. Le Corre S., Klafki HW, Plesnila N, Hübinger G, Obermeier A, Sahagún H, Monse B., Seneci P, Lewis J, Eriksen J, Zehr C, Yue M, McGowan E, Dickson D. W, Hutton M, Roder HM (2006) An inhibitor of tau hyperphosphorylation prevents severe motor impairments in tau transgenic mice. Proc Natl Acad Sci U S A 103:9673-9678. CrossRef Medline
46. Lee B. H, Lee MJ, Park S, Oh DC, Elsasser S, Chen PC, Gartner C, Dimova N, Hanna J., Gygi SP, Wilson SM, King RW, Finley D (2010) Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature 467:179-184. CrossRef Medline
47. Lee M. S, Kwon YT, Li M, Peng J, Friedlander RM, Tsai LH (2000) Neurotoxicity induces cleavage of p35 to p25 by calpain. Nature 405:360-364. CrossRef Medline
48. Lee V. M, Goedert M, Trojanowski JQ (2001) Neurodegenerative tauopathies. Annu Rev Neurosci 24:1121-1159. CrossRef Medline
49. Lein E. S, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A, Boe AF, Boguski M. S, Brockway KS, Byrnes EJ, Chen L, Chen L, Chen TM, Chin MC, Chong J, Crook BE, Czaplinska A, Dang CN, Datta S, Dee NR, et al. (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature 445:168-176. CrossRef Medline
50. Lewis J., McGowan E, Rockwood J, Melrose H, Nacharaju P, Van Slegtenhorst M, Gwinn-Hardy K, Paul Murphy M, Baker M, Yu X, Duff K, Hardy J, Corral A., Lin WL, Yen SH, Dickson DW, Davies P, Hutton M (2000) Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat Genet 25:402-405. CrossRef Medline
51. Liang B., Duan BY, Zhou XP, Gong JX, Luo ZG (2010) Calpain activation promotes BACE1 expression, amyloid precursor protein processing, and amyloid plaque formation in a transgenic mouse model of Alzheimer disease. J Biol Chem 285:27737-27744. CrossRef Medline
52. Liu L., Drouet V, Wu JW, Witter MP, Small SA, Clelland C, Duff K (2012) Trans-synaptic spread of tau pathology in vivo. PLoS One 7:e31302. CrossRef Medline
53. Lopes J. P, Agostinho P (2011) Cdk5: multitasking between physiological and pathological conditions. Prog Neurobiol 94:49-63. CrossRef Medline
54. Mandelkow E. M, Mandelkow E (2012) Biochemistry and cell biology of tau protein in neurofibrillary degeneration. Cold Spring Harb Perspect Med 2:a006247. Medline
55. Mandic A., Viktorsson K, Strandberg L, Heiden T, Hansson J, Linder S, Shoshan MC (2002) Calpain-mediated Bid cleavage and calpain-independent Bak modulation: two separate pathways in cisplatin-induced apoptosis. Mol Cell Biol 22:3003-3013. CrossRef Medline
56. Matsuoka Y., Jouroukhin Y, Gray AJ, Ma L, Hirata-Fukae C, Li HF, Feng L, Lecanu L., Walker BR, Planel E, Arancio O, Gozes I, Aisen PS (2008) A neuronal microtubule-interacting agent, NAPVSIPQ, reduces tau pathology and enhances cognitive function in a mouse model of Alzheimer's disease. J Pharmacol Exp Ther 325:146-153. CrossRef Medline
57. McCollum A. T, Jafarifar F, Lynn BC, Agu RU, Stinchcomb AL, Wang S, Chen Q, Guttmann RP (2006) Inhibition of calpain-mediated cell death by a novel peptide inhibitor. Exp Neurol 202:506-513. CrossRef Medline
58. McMillan P. J, Kraemer BC, Robinson L, Leverenz JB, Raskind M, Schellenberg G (2011) Truncation of tau at E391 promotes early pathologic changes in transgenic mice. J Neuropathol Exp Neurol 70:1006-1019. CrossRef Medline
59. Medeiros R., Kitazawa M, Chabrier MA, Cheng D, Baglietto-Vargas D, Kling A, Moeller A, Green KN, LaFerlaFM (2012) Calpain inhibitor A-705253 mitigates Alzheimer's disease-like pathology and cognitive decline in aged 3xTgAD mice. Am J Pathol 181:616-625. CrossRef Medline
60. Mercken M., Grynspan F, Nixon RA (1995) Differential sensitivity to proteolysis by brain calpain of adult human tau, fetal human tau and PHF-tau. FEBS Lett 368:10-14. CrossRef Medline
61. Nagao S., Saido TC, Akita Y, Tsuchiya T, Suzuki K, Kawashima S (1994) Calpain-calpastatin interactions in epidermoid carcinoma KB cells. J Biochem 115:1178-1184. Medline
62. Nakagawa T., Yuan J (2000) Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. J Cell Biol 150:887-894. CrossRef Medline
63. Nash K. R, Lee DC, Hunt JB Jr, Morganti JM, Selenica ML, Moran P, Reid P, Brownlow M., Guang-Yu Yang C, Savalia M, Gemma C, Bickford PC, Gordon M. N, Morgan D (2013) Fractalkine overexpression suppresses tau pathology in a mouse model of tauopathy. Neurobiol Aging 34:1540-1548. CrossRef Medline
64. Nguyen M. D, Julien JP (2003) Cyclin-dependent kinase 5 in amyotrophic lateral sclerosis. Neurosignals 12:215-220. CrossRef Medline
65. Nixon R. A (2003) The calpains in aging and aging-related diseases. Ageing Res Rev 2:407-418. CrossRef Medline
66. Nixon R. A, Saito KI, Grynspan F, Griffin WR, Katayama S, Honda T, Mohan PS, Shea TB, BeermannM (1994) Calcium-activated neutral proteinase (calpain) system in aging and Alzheimer's disease. Ann N Y Acad Sci 747:77-91. Medline
67. Ohno M., Cole SL, Yasvoina M, Zhao J, Citron M, Berry R, Disterhoft JF, Vassar R (2007) BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice. Neurobiol Dis 26:134-145. CrossRef Medline
68. Park S. Y, Ferreira A (2005) The generation of a 17 kDa neurotoxic fragment: an alternative mechanism by which tau mediates b-amyloid-induced neurodegeneration. J Neurosci 25:5365-5375. CrossRef Medline
69. Patrick G. N, Zukerberg L, Nikolic M, de la Monte S, Dikkes P, Tsai LH (1999) Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature 402:615-622. CrossRef Medline
70. Poorkaj P., Bird TD, Wijsman E, Nemens E, Garruto RM, Anderson L, Andreadis A, Wiederholt WC, Raskind M, SchellenbergGD (1998) Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann Neurol 43:815-825. CrossRef Medline
71. Rami A., Volkmann T, Agarwal R, Schoninger S, Nürnberger F, Saido TC, Winckler J. (2003) beta2-Adrenergic receptor responsiveness of the calpain-calpastatin system and attenuation of neuronal death in rat hippocampus after transient global ischemia. Neurosci Res 47:373-382. CrossRef Medline
72. Rao M. V, Campbell J, Yuan A, Kumar A, Gotow T, Uchiyama Y, Nixon RA (2003) The neurofilament middle molecular mass subunit carboxylterminal tail domains is essential for the radial growth and cytoskeletal architecture of axons but not for regulating neurofilament transport rate. J Cell Biol 163:1021-1031. CrossRef Medline
73. Rao M. V, Mohan PS, Peterhoff CM, Yang DS, Schmidt SD, Stavrides PH, Campbell J., Chen Y, Jiang Y, Paskevich PA, Cataldo AM, Haroutunian V, Nixon R. A (2008) Marked calpastatin (CAST) depletion in Alzheimer's disease accelerates cytoskeleton disruption and neurodegeneration: neuroprotection by CAST overexpression. J Neurosci 28:12241-12254. CrossRef Medline
74. Reinecke J. B, DeVos SL, McGrath JP, Shepard AM, Goncharoff DK, Tait DN, Fleming S. R, Vincent MP, Steinhilb ML (2011) Implicating calpain in tau-mediated toxicity in vivo. PLoS One 6:e23865. CrossRef Medline
75. Reith M. E, Ali S, Hashim A, Sheikh IS, Theddu N, Gaddiraju NV, Mehrotra S, Schmitt K. C, Murray TF, Sershen H, Unterwald EM, Davis FA (2012) Novel C-1 substituted cocaine analogs unlike cocaine or benztropine. J Pharmacol Exp Ther 343:413-425. CrossRef Medline
76. Sahara N., Lewis J, DeTure M, McGowan E, Dickson DW, Hutton M, Yen SH (2002) Assembly of tau in transgenic animals expressing P301L tau: alteration of phosphorylation and solubility 1017. J Neurochem 83:1498-1508. CrossRef Medline
77. Sahara N., DeTure M, Ren Y, Ebrahim AS, Kang D, Knight J, Volbracht C, Pedersen J. T, Dickson DW, Yen SH, Lewis J (2013) Characteristics of TBS-extractable hyperphosphorylated tau species: aggregation intermediates in rTg4510 mouse brain. J Alzheimers Dis 33:249-263. CrossRef Medline
78. Saito K., Elce JS, Hamos JE, Nixon RA (1993) Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration. Proc Natl Acad Sci U S A 90:2628-2632. CrossRef Medline
79. Sato K., Minegishi S, Takano J, Plattner F, Saito T, Asada A, Kawahara H, Iwata N, Saido TC, Hisanaga S (2011) Calpastatin, an endogenous calpaininhibitor protein, regulates the cleavage of the Cdk5 activator p35 to p25. J Neurochem 117:504-515. CrossRef Medline
80. Schmidt S. D, Jiang Y, Nixon RA, Mathews PM (2005) Tissue processing prior to protein analysis and amyloid-beta quantitation. Methods Mol Biol 299:267-278. Medline
81. Schoch K. M, Evans HN, Brelsfoard JM, Madathil SK, Takano J, Saido TC, Saatman K. E (2012) Calpastatin overexpression limits calpain-mediated proteolysis and behavioral deficits following traumatic brain injury. Exp Neurol 236:371-382. CrossRef Medline
82. Schoch K. M, von Reyn CR, Bian J, Telling GC, Meaney DF, Saatman KE (2013) Brain injury-induced proteolysis is reduced in a novel calpastatinoverexpressing transgenic mouse. J Neurochem 125:909-920. CrossRef Medline
83. Shea T. B (1997) Restriction of microM-calcium-requiring calpain activation to the plasma membrane in human neuroblastoma cells: evidence for regionalized influence of a calpain activator protein. J Neurosci Res 48: 543-550. CrossRef Medline
84. Shukla V., Skuntz S, Pant HC (2012) Deregulated Cdk5 activity is involved in inducing Alzheimer's disease. Arch Med Res 43:655-662. CrossRef Medline
85. Sievers S. A, Karanicolas J, Chang HW, Zhao A, Jiang L, Zirafi O, Stevens JT, Münch J., Baker D, Eisenberg D (2011) Structure-based design of nonnatural amino-acid inhibitors of amyloid fibril formation. Nature 475: 96-100. CrossRef Medline
86. Sigurdsson E. M (2014) Tau immunotherapy and imaging. Neurodegener Dis 13:103-106. CrossRef Medline
87. Simoes A. T, Goncalves N, Koeppen A, Déglon N, Kügler S, Duarte CB, Pereira de Almeida L. (2012) Calpastatin-mediated inhibition of calpains in the mouse brain prevents mutant ataxin 3 proteolysis, nuclear localization and aggregation, relieving Machado-Joseph disease. Brain 135:2428-2439. CrossRef Medline
88. Smiley J. F, Rosoklija G, Mancevski B, Pergolizzi D, Figarsky K, Bleiwas C, Duma A., Mann JJ, Javitt DC, Dwork AJ (2011) Hemispheric comparisons of neuron density in the planum temporale of schizophrenia and nonpsychiatric brains. Psychiatry Res 192:1-11. CrossRef Medline
89. Smith M. A, SchnellmannRG (2012) Calpains, mitochondria, and apoptosis. Cardiovasc Res 96:32-37. CrossRef Medline
90. Spillantini M. G, Goedert M (2013) Tau pathology and neurodegeneration. Lancet Neurol 12:609-622. CrossRef Medline
91. Su S. C, Seo J, Pan JQ, Samuels BA, Rudenko A, Ericsson M, Neve RL, Yue DT, Tsai L. H (2012) Regulation of N-type voltage-gated calcium channels and presynaptic function by cyclin-dependent kinase 5. Neuron 75:675-687. CrossRef Medline
92. Sun M., Zhao Y, Xu C (2008) Cross-talk between calpain and caspase-3 in penumbra and core during focal cerebral ischemia-reperfusion. Cell Mol Neurobiol 28:71-85. CrossRef Medline
93. Suwanjang W., Phansuwan-Pujito P, Govitrapong P, Chetsawang B (2010) The protective effect of melatonin on methamphetamine-induced calpain-dependent death pathway in human neuroblastoma SH-SY5Y cultured cells. J Pineal Res 48:94-101. CrossRef Medline
94. Takano J., Tomioka M, Tsubuki S, Higuchi M, Iwata N, Itohara S, Maki M, Saido T. C (2005) Calpain mediates excitotoxic DNA fragmentation via mitochondrial pathways in adult brains: evidence from calpastatin mutant mice. J Biol Chem 280:16175-16184. CrossRef Medline
95. Takashima A., Murayama M, Yasutake K, Takahashi H, Yokoyama M, Ishiguro K. (2001) Involvement of cyclin dependent kinase5 activator p25 on tau phosphorylation in mouse brain. Neurosci Lett 306:37-40. CrossRef Medline
96. Theunis C., Crespo-Biel N, Gafner V, Pihlgren M, López-Deber MP, Reis P, Hickman D. T, Adolfsson O, Chuard N, Ndao DM, Borghgraef P, Devijver H, Van Leuven F, Pfeifer A, Muhs A (2013) Efficacy and safety of a liposome-based vaccine against protein Tau, assessed in tau. P301L mice that model tauopathy. PLoS One 8:e72301. CrossRef Medline
97. Trinchese F., Fa M, Liu S, Zhang H, Hidalgo A, Schmidt SD, Yamaguchi H, Yoshii N., Mathews PM, Nixon RA, Arancio O (2008) Inhibition of calpains improves memory and synaptic transmission in a mouse model of Alzheimer disease. J Clin Invest 118:2796-2807. CrossRef Medline
98. Veeranna, Kaji T, Boland B, Odrljin T, Mohan P, Basavarajappa BS, Peterhoff C, Cataldo A, Rudnicki A, Amin N, Li BS, Pant HC, Hungund BL, Arancio O, Nixon RA (2004) Calpain mediates calcium-induced activation of the erk1,2 MAPK pathway and cytoskeletal phosphorylation in neurons: relevance to Alzheimer's disease. Am J Pathol 165:795-805. CrossRef Medline
99. Villalpando Rodriguez G. E, Torriglia A (2013) Calpain 1 induce lysosomal permeabilization by cleavage of lysosomal associated membrane protein 2. Biochim Biophys Acta 1833:2244-2253. CrossRef Medline
100. Walker L. C, Diamond MI, Duff KE, Hyman BT (2013) Mechanisms of protein seeding in neurodegenerative diseases. JAMA Neurol 70:304-310. CrossRef Medline
101. Wang J., Santa-Maria I, HoL, Ksiezak-Reding H, Ono K, Teplow DB, Pasinetti GM (2010) Grape derived polyphenols attenuate tau neuropathology in a mouse model of Alzheimer's disease. J Alzheimers Dis 22:653-661. CrossRef Medline
102. Wang K. K, Yuen PW (1997) Development and therapeutic potential of calpain inhibitors. Adv Pharmacol 37:117-152. Medline
103. Wang Y. P, Biernat J, Pickhardt M, Mandelkow E, Mandelkow EM (2007) Stepwise proteolysis liberates tau fragments that nucleate the Alzheimerlike aggregation of full-length tau in a neuronal cell model. Proc Natl Acad Sci U S A 104:10252-10257. CrossRef Medline
104. Ward S. M, Himmelstein DS, Lancia JK, Binder LI (2012) Tau oligomers and tau toxicity in neurodegenerative disease. Biochem Soc Trans 40:667-671. CrossRef Medline
105. Ward S. M, Himmelstein DS, Ren Y, Fu Y, Yu XW, Roberts K, Binder LI, Sahara N. (2014) TOC1: a valuable tool in assessing disease progression in the rTg4510 mouse model of tauopathy. Neurobiol Dis 67:37-48. CrossRef Medline
106. Wesson D. W, Wilson DA (2011) Age and gene overexpression interact to abolish nesting behavior in Tg2576 amyloid precursor protein (APP) mice. Behav Brain Res 216:408-413. CrossRef Medline
107. Yamashima T. (2013) Reconsider Alzheimer's disease by the 'calpaincathepsin hypothesis'-a perspective review. Prog Neurobiol 105:1-23. CrossRef Medline
108. Yanamandra K., Kfoury N, Jiang H, Mahan TE, Ma S, Maloney SE, Wozniak DF, Diamond MI, HoltzmanDM (2013) Anti-tau antibodies that block tau aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo. Neuron 80:402-414. CrossRef Medline
109. Yoshiyama Y., Higuchi M, Zhang B, Huang SM, Iwata N, Saido TC, Maeda J, Suhara T., Trojanowski JQ, Lee VM (2007) Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53:337-351. CrossRef Medline
110. Yousefi S., Perozzo R, Schmid I, Ziemiecki A, Schaffner T, Scapozza L, Brunner T, Simon HU (2006) Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat Cell Biol 8:1124-1132. CrossRef Medline
111. Yuzwa S. A, Shan X, Macauley MS, Clark T, Skorobogatko Y, Vosseller K, Vocadlo D. J (2012) Increasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation. Nat Chem Biol 8:393-399. CrossRef Medline
112. Zhang B., Carroll J, Trojanowski JQ, Yao Y, Iba M, Potuzak JS, Hogan AM, Xie SX, Ballatore C, Smith AB 3rd, Lee VM, Brunden KR (2012) The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer-like pathology in an interventional study with aged tau transgenic mice. J Neurosci 32:3601-3611. CrossRef Medline