Screening strategies to identify HSP70 modulators to treat Alzheimer’s disease

Drug Design, Development and Therapy

Volumn 9, Issue , 2015, Pages 321-331

  Repalli, Jayanthi ^a   Meruelo, Daniel ^a  

^a NEW YORK UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Adenosine triphosphatase activity; Aggregation; Beta amyloid; Heat shock protein 70; Oligomers; Tau

Indexed keywords

1 ETHYL 2 [[3 ETHYL 5 (3 METHYLBENZOTHIAZOLIN 2 YLIDENE) 4 OXOTHIAZOLIDIN 2 YLIDENE]METHYL]PYRIDINIUM CHLORIDE; 113F 08; 330B 06; ADENOSINE TRIPHOSPHATASE; AGENTS AFFECTING PROTEIN METABOLISM; AMINOTHIENOPYRIDAZINE DERIVATIVE; AMYLOID BETA PROTEIN; HEAT SHOCK PROTEIN 70; HEAT SHOCK PROTEIN 70 MODULATOR; METHYLENE BLUE; PYRIDAZINE DERIVATIVE; TAU PROTEIN; TEPRENONE; THIOFLAVINE; UNCLASSIFIED DRUG; YM 01; YM 08; ENZYME INHIBITOR; NEUROPROTECTIVE AGENT; PROTEASOME; PROTEIN AGGREGATE;

ALZHEIMER DISEASE; BINDING ASSAY; CELL ASSAY; CELL CULTURE; COLORIMETRY; DRUG CLEARANCE; DRUG IDENTIFICATION; DRUG PROTEIN BINDING; DRUG RETENTION; DRUG SCREENING; DRUG TARGETING; ENZYME LINKED IMMUNOSORBENT ASSAY; FLUORESCENCE ANALYSIS; FLUORESCENCE POLARIZATION; HIGH THROUGHPUT SCREENING; HUMAN; LUCIFERASE ASSAY; NONHUMAN; OLIGOMERIZATION; PROTEIN AGGREGATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; RADIOMETRY; REVIEW; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DEVELOPMENT; METABOLISM; MOLECULARLY TARGETED THERAPY; PROCEDURES; PROTEIN FOLDING; STRUCTURE ACTIVITY RELATION;

ADENOSINE TRIPHOSPHATASES; ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; DRUG DISCOVERY; ENZYME INHIBITORS; HIGH-THROUGHPUT SCREENING ASSAYS; HSP70 HEAT-SHOCK PROTEINS; HUMANS; MOLECULAR STRUCTURE; MOLECULAR TARGETED THERAPY; NEUROPROTECTIVE AGENTS; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEIN AGGREGATES; PROTEIN FOLDING; STRUCTURE-ACTIVITY RELATIONSHIP; TAU PROTEINS;

EID: 84920928078     PISSN: 11778881     EISSN: 11778881     Source Type: Journal    
DOI: 10.2147/DDDT.S72165     Document Type: Review

References (82)

1. Alzheimer’s Association. Alzheimer’s disease facts and figures. Alzheimers Dement. 2014;10(2):e47-e92.
2. Kumar S, Walter J. Phosphorylation of amyloid beta (Abeta) peptides-a trigger for formation of toxic aggregates in Alzheimer’s disease. Aging (Albany NY). 2011;3(8):803-812.
3. Mattson MP. Pathways towards and away from Alzheimer’s disease. Nature. 2004;430(7000):631-639.
4. Sakono M, Zako T. Amyloid oligomers: formation and toxicity of Abeta oligomers. FEBS J. 2010;277(6):1348-1358.
5. Kim HJ, Chae SC, Lee DK, et al. Selective neuronal degeneration induced by soluble oligomeric amyloid beta protein. FASEB J. 2003;17(1): 118-120.
6. Takashima A. Amyloid-beta, tau, and dementia. J Alzheimers Dis. 2009;17(4):729-736.
7. Dolan D, Troncoso J, Resnick SM, Crain BJ, Zonderman AB, O’Brien RJ. Age, Alzheimer’s disease and dementia in the BaltimoreLongitudinal Study of Ageing. Brain. 2010;133 Pt 8:2225-2231.
8. Dolan H, Crain B, Troncoso J, Resnick SM, Zonderman AB, O’Brien RJ. Atherosclerosis, dementia, and Alzheimer disease in the Baltimore Longitudinal Study of Aging cohort. Ann Neurol. 2010;68(2): 231-240.
9. O’Brien RJ, Wong PC. Amyloid precursor protein processing and Alzheimer’s disease. Annu Rev Neurosci. 2011;34:185-204.
10. Medina M, Avila J. The role of extracellular Tau in the spreading of neurofibrillary pathology. Front Cell Neurosci. 2014;8:113.
11. Walsh DM, Selkoe DJ. Oligomers on the brain: the emerging role of soluble protein aggregates in neurodegeneration. Protein Pept Lett. 2004;11(3):213-228.
12. Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med. 2011;1(1):a006189.
13. Huang Y, Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell. 2012;148(6):1204-1222.
14. Turturici G, Sconzo G, Geraci F. HSP70 and its molecular role in nervous system diseases. Biochem Res Int. 2011;2011:618127.
15. Mayer MP, Bukau B. HSP70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci. 2005;62(6):670-684.
16. Liberek K, Lewandowska A, Zietkiewicz S. Chaperones in control of protein disaggregation. EMBO J. 2008;27(2):328-335.
17. Evans CG, Wisen S, Gestwicki JE. Heat shock proteins 70 and 90 inhibit early stages of amyloid beta-(1-42) aggregation in vitro. J Biol Chem. 2006;281(44):33182-33191.
18. Jinwal UK, Miyata Y, Koren J,3rd, et al. Chemical manipulation of HSP70 ATPase activity regulates tau stability. J Neurosci. 2009;29(39): 12079-12088.
19. Voss K, Combs B, Patterson KR, Binder LI, Gamblin TC. HSP70 alters tau function and aggregation in an isoform specific manner. Biochemistry. 2012;51(4):888-898.
20. Cyr DM, Hohfeld J, Patterson C. Protein quality control: U-boxcontaining E3 ubiquitin ligases join the fold. Trends Biochem Sci. 2002; 27(7):368-375.
21. Jiang J, Ballinger CA, Wu Y, et al. CHIP is a U-box-dependent E3 ubiquitin ligase: identification of HSC70 as a target for ubiquitylation. J Biol Chem. 2001;276(46):42938-42944.
22. Perez N, Sugar J, Charya S, et al. Increased synthesis and accumulation of heat shock 70 proteins in Alzheimer’s disease. Brain Res Mol Brain Res. 1991;11(3-4):249-254.
23. Labrador-Garrido A, Bertoncini CW, Roodveldt C. The HSP70 chaperone system in Parkinson’s disease. In: Rana AQ, editor. Etiology and Pathophysiology of Parkinson’s disease. Available from: http://www.intechopen.com/books/etiology-and-pathophysiology-of-parkinson-s-isease/the-hsp70-chaperone-system-in-parkinson-s-disease.
24. Mayer RJ, Arnold J, Laszlo L, Landon M, Lowe J. Ubiquitin in health and disease. Biochim Biophys Acta. 1991;1089(2):141-157.
25. Fernandez-Estevez MA, Casarejos MJ, Lopez Sendon J, et al. Trehalose reverses cell malfunction in fibroblasts from normal and Huntington’s disease patients caused by proteosome inhibition. PLoS One. 2014;9(2): e90202.
26. Hoshino T, Murao N, Namba T, et al. Suppression of Alzheimer’s disease-related phenotypes by expression of heat shock protein 70 in mice. J Neurosci. 2011;31(14):5225-5234.
27. Kakimura J, Kitamura Y, Takata K, et al. Microglial activation and amyloid-beta clearance induced by exogenous heat-shock proteins. FASEB J. 2002;16(6):601-603.
28. Petrucelli L, Dickson D, Kehoe K, et al. CHIP and HSP70 regulate tau ubiquitination, degradation and aggregation. Hum Mol Genet. 2004;13(7): 703-714.
29. Fewell SW, Smith CM, Lyon MA, et al. Small molecule modulators of endogenous and co-chaperone-stimulated HSP70 ATPase activity. J Biol Chem. 2004;279(49):51131-51140.
30. McCarty JS, Buchberger A, Reinstein J, Bukau B. The role of ATP in the functional cycle of the DnaK chaperone system. J Mol Biol. 1995;249(1): 126-137.
31. Nadler SG, Eversole AC, Tepper MA, Cleaveland JS. Elucidating the mechanism of action of the immunosuppressant 15-deoxyspergualin. Ther Drug Monit. 1995;17(6):700-703.
32. Brodsky JL. Selectivity of the molecular chaperone-specific immunosuppressive agent 15-deoxyspergualin: modulation of HSC70 ATPase activity without compromising DnaJ chaperone interactions. Biochem Pharmacol. 1999;57(8):877-880.
33. Cogan EB, Birrell GB, Griffith OH. A robotics-based automated assay for inorganic and organic phosphates. Anal Biochem. 1999;271(1):29-35.
34. Chang L, Bertelsen EB, Wisen S, Larsen EM, Zuiderweg ER, Gestwicki JE. High-throughput screen for small molecules that modulate the ATPase activity of the molecular chaperone DnaK. Anal Biochem. 2008;372(2):167-176.
35. Miyata Y, Chang L, Bainor A, et al. High-throughput screen for Escherichia coli heat shock protein 70 (HSP70/DnaK): ATPase assay in low volume by exploiting energy transfer. J Biomol Screen. 2010;15(10): 1211-1219.
36. Zuck P, O’Donnell GT, Cassaday J, et al. Miniaturization of absorbance assays using the fluorescent properties of white microplates. Anal Biochem. 2005;342(2):254-259.
37. Kang Y, Taldone T, Clement CC, et al. Design of a fluorescence polarization assay platform for the study of human HSP70. Bioorg Med Chem Lett. 2008;18(13):3749-3751.
38. Ricci L, Williams KP. Development of fluorescence polarization assays for the molecular chaperone HSP70 family members: HSP72 and DnaK. Curr Chem Genomics. 2008;2:90-95.
39. Wisen S, Gestwicki JE. Identification of small molecules that modify the protein folding activity of heat shock protein 70. Anal Biochem. 2008; 374(2):371-377.
40. Thulasiraman V, Matts RL. Luciferase renaturation assays of chaperones and chaperone antagonists. Methods Mol Biol. 1998;102: 129-141.
41. Frydman J, Hartl FU. Principles of chaperone-assisted protein folding: differences between in vitro and in vivo mechanisms. Science. 1996; 272(5267):1497-1502.
42. Frydman J, Nimmesgern E, Ohtsuka K, Hartl FU. Folding of nascent polypeptide chains in a high molecular mass assembly with molecular chaperones. Nature. 1994;370(6485):111-117.
43. Schumacher RJ, Hurst R, Sullivan WP, McMahon NJ, Toft DO, Matts RL. ATP-dependent chaperoning activity of reticulocyte lysate. J Biol Chem. 1994;269(13):9493-9499.
44. Thulasiraman V, Matts RL. Effect of geldanamycin on the kinetics of chaperone-mediated renaturation of firefly luciferase in rabbit reticulocyte lysate. Biochemistry. 1996;35(41):13443-13450.
45. Wawrzynow A, Zylicz M. Divergent effects of ATP on the binding of the DnaK and DnaJ chaperones to each other, or to their various native and denatured protein substrates. J Biol Chem. 1995;270(33): 19300-19306.
46. Ha JH, McKay DB. Kinetics of nucleotide-induced changes in the tryptophan fluorescence of the molecular chaperone HSC70 and its subfragments suggest the ATP-induced conformational change follows initial ATP binding. Biochemistry. 1995;34(36):11635-11644.
47. Hawe A, Sutter M, Jiskoot W. Extrinsic fluorescent dyes as tools for protein characterization. Pharm Res. 2008;25(7):1487-1499.
48. Bolder SG, Sagis LM, Venema P, van der Linden E. Thioflavin T and birefringence assays to determine the conversion of proteins into fibrils. Langmuir. 2007;23(8):4144-4147.
49. Hudson SA, Ecroyd H, Kee TW, Carver JA. The thioflavin T fluorescence assay for amyloid fibril detection can be biased by the presence of exogenous compounds. FEBS J. 2009;276(20):5960-5972.
50. Zhang H Xu LQ, Perrett S. Studying the effects of chaperones on amyloid fibril formation. Methods. 2011;53(3):285-294.
51. LeVine H. 3rd. Thioflavine T interaction with synthetic Alzheimer’s disease beta-amyloid peptides: detection of amyloid aggregation in solution. Protein Sci. 1993;2(3):404-410.
52. Nilsson MR. Techniques to study amyloid fibril formation in vitro. Methods. 2004;34(1):151-160.
53. Eisert R, Felau L, Brown LR. Methods for enhancing the accuracy and reproducibility of Congo red and thioflavin T assays. Anal Biochem. 2006; 353(1):144-146.
54. Krebs MR, Bromley EH, Donald AM. The binding of thioflavin-T to amyloid fibrils: localisation and implications. J Struct Biol. 2005; 149(1):30-37.
55. Crowe A, Ballatore C, Hyde E, Trojanowski JQ, Lee VM. High throughput screening for small molecule inhibitors of heparin-induced tau fibril formation. Biochem Biophys Res Commun. 2007;358(1):1-6.
56. Crowe A, Huang W, Ballatore C, et al. Identification of aminothienopyridazine inhibitors of tau assembly by quantitative highthroughput screening. Biochemistry. 2009;48(32):7732-7745.
57. Patterson KR, Ward SM, Combs B, et al. Heat shock protein 70 prevents both tau aggregation and the inhibitory effects of preexisting tau aggregates on fast axonal transport. Biochemistry. 2011;50(47): 10300-10310.
58. Khlistunova I, Pickhardt M, Biernat J, Wang Y, Mandelkow E., Mandelkow E. Inhibition of tau aggregation in cell models of tauopathy. Curr Alzheimer Res. 2007;4(5):544-546.
59. Khlistunova I, Biernat J, Wang Y, et al. Inducible expression of Tau repeat domain in cell models of tauopathy: aggregation is toxic to cells but can be reversed by inhibitor drugs. J Biol Chem. 2006;281(2):1205-1214.
60. Santa-Maria I, Perez M, Hernandez F, Avila J, Moreno FJ. Characteristics of the binding of thioflavin S to tau paired helical filaments. J Alzheimers Dis. 2006;9(3):279-285.
61. Lee LL, Ha H, Chang YT, DeLisa MP. Discovery of amyloid-beta aggregation inhibitors using an engineered assay for intracellular protein folding and solubility. Protein Sci. 2009;18(2):277-286.
62. Fisher AC, Kim W, DeLisa MP. Genetic selection for protein solubility enabled by the folding quality control feature of the twin-arginine translocation pathway. Protein Sci. 2006;15(3):449-458.
63. Park SK, Pegan SD, Mesecar AD, Jungbauer LM, LaDu MJ, Liebman SW. Development and validation of a yeast high-throughput screen for inhibitors of Abeta(4)(2) oligomerization. Dis Model Mech. 2011;4(6):822-831.
64. Hall AM, Roberson ED. Mouse models of Alzheimer’s disease. Brain Res Bull. 2012;88(1):3-12.
65. Bryan KJ, Lee H, Perry G, Smith MA, Casadesus G. Transgenic mouse models of Alzheimer’s disease: behavioral testing and considerations. In: Buccafusco JJ, editor. Methods of Behavior Analysis in Neuroscience. Boca Raton, FL, USA: CRC Press; 2009.
66. Hoshino T, Suzuki K, Matsushima T, Yamakawa N, Suzuki T, Mizushima T. Suppression of Alzheimer’s disease-related phenotypes by geranylgeranylacetone in mice. PLoS One. 2013;8(10):e76306.
67. Miyata Y, Li X, Lee HF, et al. Synthesis and initial evaluation of YM-08, a blood-brain barrier permeable derivative of the heat shock protein 70 (HSP70) inhibitor MKT-077, which reduces tau levels. ACS Chem Neurosci. 2013;4(6):930-939
68. Miyata Y, Koren J, Kiray J, Dickey CA, Gestwicki JE. Molecular chaperones and regulation of tau quality control: strategies for drug discovery in tauopathies. Future Med Chem. 2011;3(12):1523-1537.
69. Miyata Y, Rauch JN, Jinwal UK, et al. Cysteine reactivity distinguishes redox sensing by the heat-inducible and constitutive forms of heat shock protein 70. Chem Biol. 2012;19(11):1391-1399.
70. Medina DX, Caccamo A, Oddo S. Methylene blue reduces abeta levels and rescues early cognitive deficit by increasing proteasome activity. Brain Pathol. 2011;21(2):140-149.
71. Wischik C BP, Wischik D, Seng K. Tau aggregation inhibitor (TAI) therapy with Rember™ arrests disease progression in mild and moderate Alzheimer’s disease over 50 weeks. Alzheimers Dement. 2008:T167.
72. Oz M, Lorke DE, Hasan M, Petroianu GA. Cellular and molecular actions of methylene blue in the nervous system. Med Res Rev. 2011; 31(1):93-117.
73. Abisambra J, Jinwal UK, Miyata Y, et al. Allosteric heat shock protein 70 inhibitors rapidly rescue synaptic plasticity deficits by reducingaberrant tau. Biol Psychiatry. 2013;74(5):367-374.
74. Wadhwa R, Sugihara T, Yoshida A, et al. Selective toxicity of MKT-077 to cancer cells is mediated by its binding to the HSP70 family protein mot-2 and reactivation of p53 function. Cancer Res. 2000;60(24):6818-6821.
75. Koya K, Li Y, Wang H, et al. MKT-077, a novel rhodacyanine dye in clinical trials, exhibits anticarcinoma activity in preclinical studies basedon selective mitochondrial accumulation. Cancer Res. 1996;56(3): 538-543.
76. Propper DJ, Braybrooke JP, Taylor DJ, et al. Phase I trial of the selective mitochondrial toxin MKT077 in chemo-resistant solid tumours. Ann Oncol. 1999;10(8):923-927.
77. Wang AM, Miyata Y, Klinedinst S, et al. Activation of HSP70 reduces neurotoxicity by promoting polyglutamine protein degradation. Nat Chem Biol. 2013;9(2):112-118.
78. O’Leary JC,3rd, Li Q, Marinec P, et al. Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden. Mol Neurodegener. 2010;5:45.
79. Marcinowski M, Rosam M, Seitz C, et al. Conformational selection in substrate recognition by HSP70 chaperones. J Mol Biol. 2013;425(3): 466-474.
80. Shiber A, Breuer W, Brandeis M, Ravid T. Ubiquitin conjugation triggers misfolded protein sequestration into quality control foci when HSP70 chaperone levels are limiting. Mol Biol Cell. 2013;24(13): 2076-2087.
81. Vanitha Thulasiraman RGF, Frydman J. Folding assays. In: Schneider C, editor. Methods in Molecular Biology. Chaperonin Protocols. Volume 140. Totowa, NJ, USA: Humana Press Inc; 2000.
82. Chang CY. High Throughput Screens Against Heat Shock Protein 70 (HSP70), University of Michigan; 2011.