The role of molecular chaperones in human misfolding diseases

FEBS Letters

Volumn 583, Issue 16, 2009, Pages 2647-2653

  Broadley, Sarah A ^a   Hartl, F Ulrich ^a  

^a MAX PLANCK INSTITUTE OF BIOCHEMISTRY   (Germany)

Author keywords

Heat shock protein; Molecular chaperone; Neurodegeneration; Protein misfolding

Indexed keywords

17 DEMETHOXY 17 (2 DIMETHYLAMINOETHYLAMINO)GELDANAMYCIN; ALPHA SYNUCLEIN; AMYLOID; ARIMOCLOMOL; CELASTROL; CHAPERONE; CHAPERONIN; GELDANAMYCIN; HEAT SHOCK PROTEIN 70; HUNTINGTIN; NOVOBIOCIN; RESVERATROL; TANESPIMYCIN; TAU PROTEIN;

ALZHEIMER DISEASE; CALORIC RESTRICTION; CLINICAL TRIAL; CONFORMATIONAL TRANSITION; DRUG MECHANISM; GENE OVEREXPRESSION; HOMEOSTASIS; HUMAN; HUNTINGTON CHOREA; NERVE DEGENERATION; NEUROTOXICITY; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN ANALYSIS; PROTEIN CONFORMATION; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN SYNTHESIS; SHORT SURVEY;

CHAPERONINS; HSP70 HEAT-SHOCK PROTEINS; HUMANS; MOLECULAR CHAPERONES; NEURODEGENERATIVE DISEASES; PROTEIN FOLDING;

EID: 68649113747     PISSN: 00145793     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.febslet.2009.04.029     Document Type: Short Survey

References (107)

1. Hartl F.U., and Hayer-Hartl M. Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295 (2002) 1852-1858
2. Bukau B., Weissman J., and Horwich A. Molecular chaperones and protein quality control. Cell 125 (2006) 443-451
3. Morimoto R.I. Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and aging. Genes Dev. 22 (2008) 1427-1438
4. Chiti F., and Dobson C.M. Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem. 75 (2006) 333-366
5. Lim J., Crespo-Barreto J., Jafar-Nejad P., Bowman A.B., Richman R., Hill D.E., Orr H.T., and Zoghbi H.Y. Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1. Nature 452 (2008) 713-718
6. Schiffer N.W., Ceraline J., Hartl F.U., and Broadley S.A. N-terminal polyglutamine-containing fragments inhibit androgen receptor transactivation function. Biol. Chem. 389 (2008) 1455-1466
7. Poirier M.A., Li H., Macosko J., Cai S., Amzel M., and Ross C.A. Huntingtin spheroids and protofibrils as precursors in polyglutamine fibrilization. J. Biol. Chem. 277 (2002) 41032-41037
8. Wacker J.L., Zareie M.H., Fong H., Sarikaya M., and Muchowski P.J. Hsp70 and Hsp40 attenuate formation of spherical and annular polyglutamine oligomers by partitioning monomer. Nat. Struct. Mol. Biol. 11 (2004) 1215-1222
9. Gosal W.S., Morten I.J., Hewitt E.W., Smith D.A., Thomson N.H., and Radford S.E. Competing pathways determine fibril morphology in the self-assembly of beta2-microglobulin into amyloid. J. Mol. Biol. 351 (2005) 850-864
10. Nagai Y., et al. A toxic monomeric conformer of the polyglutamine protein. Nat. Struct. Mol. Biol. 14 (2007) 332-340
11. Dedmon M.M., Christodoulou J., Wilson M.R., and Dobson C.M. Heat shock protein 70 inhibits alpha-synuclein fibril formation via preferential binding to prefibrillar species. J. Biol. Chem. 280 (2005) 14733-14740
12. Arrasate M., Mitra S., Schweitzer E.S., Segal M.R., and Finkbeiner S. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431 (2004) 805-810
13. Schaffar G., et al. Cellular toxicity of polyglutamine expansion proteins: mechanism of transcription factor deactivation. Mol. Cell 15 (2004) 95-105
14. Muchowski P.J., and Wacker J.L. Modulation of neurodegeneration by molecular chaperones. Nat. Rev. Neurosci. 6 (2005) 11-22
15. Kayed R., Head E., Thompson J.L., McIntire T.M., Milton S.C., Cotman C.W., and Glabe C.G. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300 (2003) 486-489
16. Tompkins M.M., and Hill W.D. Contribution of somal Lewy bodies to neuronal death. Brain Res. 775 (1997) 24-29
17. Auluck P.K., and Bonini N.M. Pharmacological prevention of Parkinson disease in Drosophila. Nat. Med. 8 (2002) 1185-1186
18. Katzman R., Terry R., DeTeresa R., Brown T., Davies P., Fuld P., Renbing X., and Peck A. Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. Ann. Neurol. 23 (1988) 138-144
19. Williams A.J., and Paulson H.L. Polyglutamine neurodegeneration: protein misfolding revisited. Trends Neurosci. 31 (2008) 521-528
20. Caughey B., and Lansbury P.T. Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders. Annu. Rev. Neurosci. 26 (2003) 267-298
21. Volles M.J., and Lansbury Jr. P.T. Zeroing in on the pathogenic form of alpha-synuclein and its mechanism of neurotoxicity in Parkinson's disease. Biochemistry 42 (2003) 7871-7878
22. Friedman M.J., Shah A.G., Fang Z.H., Ward E.G., Warren S.T., Li S., and Li X.J. Polyglutamine domain modulates the TBP-TFIIB interaction: implications for its normal function and neurodegeneration. Nat. Neurosci. 10 (2007) 1519-1528
23. Balch W.E., Morimoto R.I., Dillin A., and Kelly J.W. Adapting proteostasis for disease intervention. Science 319 (2008) 916-919
24. Mayer M.P., and Bukau B. Hsp70 chaperones: cellular functions and molecular mechanism. Cell Mol. Life Sci. 62 (2005) 670-684
25. Goloubinoff P., and De Los Rios P. The mechanism of Hsp70 chaperones: (entropic) pulling the models together. Trends Biochem. Sci. 32 (2007) 372-380
26. Luders J., Demand J., and Hohfeld J. The ubiquitin-related BAG-1 provides a link between the molecular chaperones Hsc70/Hsp70 and the proteasome. J. Biol. Chem. 275 (2000) 4613-4617
27. Gamerdinger M., Hajieva P., Kaya A.M., Wolfrum U., Hartl F.U., and Behl C. Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3. EMBO J. 28 (2009) 889-901
28. Demand J., Alberti S., Patterson C., and Hohfeld J. Cooperation of a ubiquitin domain protein and an E3 ubiquitin ligase during chaperone/proteasome coupling. Curr. Biol. 11 (2001) 1569-1577
29. Shin Y., Klucken J., Patterson C., Hyman B.T., and McLean P.J. The co-chaperone carboxyl terminus of Hsp70-interacting protein (CHIP) mediates alpha-synuclein degradation decisions between proteasomal and lysosomal pathways. J. Biol. Chem. 280 (2005) 23727-23734
30. Shaner L., Wegele H., Buchner J., and Morano K.A. The yeast Hsp110 Sse1 functionally interacts with the Hsp70 chaperones Ssa and Ssb. J. Biol. Chem. 280 (2005) 41262-41269
31. Shaner L., Sousa R., and Morano K.A. Characterization of Hsp70 binding and nucleotide exchange by the yeast Hsp110 chaperone Sse1. Biochemistry 45 (2006) 15075-15084
32. Polier S., Dragovic Z., Hartl F.U., and Bracher A. Structural basis for the cooperation of Hsp70 and Hsp110 chaperones in protein folding. Cell 133 (2008) 1068-1079
33. Senderek J., et al. Mutations in SIL1 cause Marinesco-Sjogren syndrome, a cerebellar ataxia with cataract and myopathy. Nat. Genet. 37 (2005) 1312-1314
34. Barral J.M., Broadley S.A., Schaffar G., and Hartl F.U. Roles of molecular chaperones in protein misfolding diseases. Semin. Cell Dev. Biol. 15 (2004) 17-29
35. Kim S., Nollen E.A., Kitagawa K., Bindokas V.P., and Morimoto R.I. Polyglutamine protein aggregates are dynamic. Nat. Cell Biol. 4 (2002) 826-831
36. Gidalevitz T., Ben-Zvi A., Ho K.H., Brignull H.R., and Morimoto R.I. Progressive disruption of cellular protein folding in models of polyglutamine diseases. Science 311 (2006) 1471-1474
37. Kaarniranta K., Oksala N., Karjalainen H.M., Suuronen T., Sistonen L., Helminen H.J., Salminen A., and Lammi M.J. Neuronal cells show regulatory differences in the hsp70 gene response. Brain Res. Mol. Brain Res. 101 (2002) 136-140
38. Marcuccilli C.J., Mathur S.K., Morimoto R.I., and Miller R.J. Regulatory differences in the stress response of hippocampal neurons and glial cells after heat shock. J. Neurosci. 16 (1996) 478-485
39. Lu T., Pan Y., Kao S.Y., Li C., Kohane I., Chan J., and Yankner B.A. Gene regulation and DNA damage in the ageing human brain. Nature 429 (2004) 883-891
40. Heydari A.R., You S., Takahashi R., Gutsmann-Conrad A., Sarge K.D., and Richardson A. Age-related alterations in the activation of heat shock transcription factor 1 in rat hepatocytes. Exp. Cell Res. 256 (2000) 83-93
41. Tonkiss J., and Calderwood S.K. Regulation of heat shock gene transcription in neuronal cells. Int. J. Hyperthermia 21 (2005) 433-444
42. Liu A.Y., Lin Z., Choi H.S., Sorhage F., and Li B. Attenuated induction of heat shock gene expression in aging diploid fibroblasts. J. Biol. Chem. 264 (1989) 12037-12045
43. Morley J.F., Brignull H.R., Weyers J.J., and Morimoto R.I. The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 99 (2002) 10417-10422
44. Parker J.A., Arango M., Abderrahmane S., Lambert E., Tourette C., Catoire H., and Neri C. Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nat. Genet. 37 (2005) 349-350
45. Cohen E., Bieschke J., Perciavalle R.M., Kelly J.W., and Dillin A. Opposing activities protect against age-onset proteotoxicity. Science 313 (2006) 1604-1610
46. Satyal S.H., Schmidt E., Kitagawa K., Sondheimer N., Lindquist S., Kramer J.M., and Morimoto R.I. Polyglutamine aggregates alter protein folding homeostasis in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 97 (2000) 5750-5755
47. Duennwald M.L., and Lindquist S. Impaired ERAD and ER stress are early and specific events in polyglutamine toxicity. Genes Dev. 22 (2008) 3308-3319
48. Magrane J., Rosen K.M., Smith R.C., Walsh K., Gouras G.K., and Querfurth H.W. Intraneuronal beta-amyloid expression downregulates the Akt survival pathway and blunts the stress response. J. Neurosci. 25 (2005) 10960-10969
49. Tagawa K., et al. The induction levels of heat shock protein 70 differentiate the vulnerabilities to mutant huntingtin among neuronal subtypes. J. Neurosci. 27 (2007) 868-880
50. Hay D.G., et al. Progressive decrease in chaperone protein levels in a mouse model of Huntington's disease and induction of stress proteins as a therapeutic approach. Hum. Mol. Genet. 13 (2004) 1389-1405
51. Cowan K.J., Diamond M.I., and Welch W.J. Polyglutamine protein aggregation and toxicity are linked to the cellular stress response. Hum. Mol. Genet. 12 (2003) 1377-1391
52. Sugars K.L., Brown R., Cook L.J., Swartz J., and Rubinsztein D.C. Decreased cAMP response element-mediated transcription: an early event in exon 1 and full-length cell models of Huntington's disease that contributes to polyglutamine pathogenesis. J. Biol. Chem. 279 (2004) 4988-4999
53. Yamanaka T., Miyazaki H., Oyama F., Kurosawa M., Washizu C., Doi H., and Nukina N. Mutant Huntingtin reduces HSP70 expression through the sequestration of NF-Y transcription factor. EMBO J. 27 (2008) 827-839
54. Iwata A., Miura S., Kanazawa I., Sawada M., and Nukina N. Alpha-Synuclein forms a complex with transcription factor Elk-1. J. Neurochem. 77 (2001) 239-252
55. Sugars K.L., and Rubinsztein D.C. Transcriptional abnormalities in Huntington disease. Trends Genet. 19 (2003) 233-238
56. Hands S., Sinadinos C., and Wyttenbach A. Polyglutamine gene function and dysfunction in the ageing brain. Biochim. Biophys. Acta 1779 (2008) 507-521
57. Rochet J.C. Novel therapeutic strategies for the treatment of protein-misfolding diseases. Expert Rev. Mol. Med. 9 (2007) 1-34
58. Magrane J., Smith R.C., Walsh K., and Querfurth H.W. Heat shock protein 70 participates in the neuroprotective response to intracellularly expressed beta-amyloid in neurons. J. Neurosci. 24 (2004) 1700-1706
59. Wu, Y., Cao, Z., Klein, W.L. and Luo, Y. (2008) Heat shock treatment reduces beta amyloid toxicity in vivo by diminishing oligomers. Neurobiol. Aging, in press. doi:10.1016/j.neurobiolaging.2008.07.013.
60. Dou F., et al. Chaperones increase association of tau protein with microtubules. Proc. Natl. Acad. Sci. USA 100 (2003) 721-726
61. Klucken J., Shin Y., Masliah E., Hyman B.T., and McLean P.J. Hsp70 reduces alpha-synuclein aggregation and toxicity. J. Biol. Chem. 279 (2004) 25497-25502
62. Rambold A.S., Miesbauer M., Rapaport D., Bartke T., Baier M., Winklhofer K.F., and Tatzelt J. Association of Bcl-2 with misfolded prion protein is linked to the toxic potential of cytosolic PrP. Mol. Biol. Cell 17 (2006) 3356-3368
63. Muchowski P.J., Schaffar G., Sittler A., Wanker E.E., Hayer-Hartl M.K., and Hartl F.U. Hsp70 and hsp40 chaperones can inhibit self-assembly of polyglutamine proteins into amyloid-like fibrils. Proc. Natl. Acad. Sci. USA 97 (2000) 7841-7846
64. Meriin A.B., Zhang X., He X., Newnam G.P., Chernoff Y.O., and Sherman M.Y. Huntington toxicity in yeast model depends on polyglutamine aggregation mediated by a prion-like protein Rnq1. J. Cell Biol. 157 (2002) 997-1004
65. Chai Y., Koppenhafer S.L., Bonini N.M., and Paulson H.L. Analysis of the role of heat shock protein (Hsp) molecular chaperones in polyglutamine disease. J. Neurosci. 19 (1999) 10338-10347
66. Jana N.R., Tanaka M., Wang G., and Nukina N. Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicity. Hum. Mol. Genet. 9 (2000) 2009-2018
67. Wyttenbach A., Sauvageot O., Carmichael J., Diaz-Latoud C., Arrigo A.P., and Rubinsztein D.C. Heat shock protein 27 prevents cellular polyglutamine toxicity and suppresses the increase of reactive oxygen species caused by huntingtin. Hum. Mol. Genet. 11 (2002) 1137-1151
68. Howarth J.L., et al. Hsp40 molecules that target to the ubiquitin-proteasome system decrease inclusion formation in models of polyglutamine disease. Mol. Ther. 15 (2007) 1100-1105
69. Miller V.M., et al. CHIP suppresses polyglutamine aggregation and toxicity in vitro and in vivo. J. Neurosci. 25 (2005) 9152-9161
70. Jana N.R., Dikshit P., Goswami A., Kotliarova S., Murata S., Tanaka K., and Nukina N. Co-chaperone CHIP associates with expanded polyglutamine protein and promotes their degradation by proteasomes. J. Biol. Chem. 280 (2005) 11635-11640
71. Al-Ramahi I., et al. CHIP protects from the neurotoxicity of expanded and wild-type ataxin-1 and promotes their ubiquitination and degradation. J. Biol. Chem. 281 (2006) 26714-26724
72. Tetzlaff J.E., Putcha P., Outeiro T.F., Ivanov A., Berezovska O., Hyman B.T., and McLean P.J. CHIP targets toxic alpha-Synuclein oligomers for degradation. J. Biol. Chem. 283 (2008) 17962-17968
73. Choi J.Y., et al. Co-chaperone CHIP promotes aggregation of ataxin-1. Mol. Cell Neurosci. 34 (2007) 69-79
74. Kumar P., et al. CHIP and HSPs interact with beta-APP in a proteasome-dependent manner and influence Abeta metabolism. Hum. Mol. Genet. 16 (2007) 848-864
75. Shimura H., Schwartz D., Gygi S.P., and Kosik K.S. CHIP-Hsc70 complex ubiquitinates phosphorylated tau and enhances cell survival. J. Biol. Chem. 279 (2004) 4869-4876
76. Jana N.R., and Nukina N. BAG-1 associates with the polyglutamine-expanded huntingtin aggregates. Neurosci. Lett. 378 (2005) 171-175
77. Yamashita H., et al. Heat-shock protein 105 interacts with and suppresses aggregation of mutant Cu/Zn superoxide dismutase: clues to a possible strategy for treating ALS. J. Neurochem. 102 (2007) 1497-1505
78. Wang J., et al. Progressive aggregation despite chaperone associations of a mutant SOD1-YFP in transgenic mice that develop ALS. Proc. Natl. Acad. Sci. USA 106 (2009) 1392-1397
79. Ishihara K., Yamagishi N., Saito Y., Adachi H., Kobayashi Y., Sobue G., Ohtsuka K., and Hatayama T. Hsp105alpha suppresses the aggregation of truncated androgen receptor with expanded CAG repeats and cell toxicity. J. Biol. Chem. 278 (2003) 25143-25150
80. Evans C.G., Wisen S., and Gestwicki J.E. Heat shock proteins 70 and 90 inhibit early stages of amyloid beta-(1-42) aggregation in vitro. J. Biol. Chem. 281 (2006) 33182-33191
81. Luk K.C., Mills I.P., Trojanowski J.Q., and Lee V.M. Interactions between Hsp70 and the hydrophobic core of alpha-synuclein inhibit fibril assembly. Biochemistry 47 (2008) 12614-12625
82. Behrends C., et al. Chaperonin TRiC promotes the assembly of polyQ expansion proteins into nontoxic oligomers. Mol. Cell 23 (2006) 887-897
83. Magen D., et al. Mitochondrial hsp60 chaperonopathy causes an autosomal-recessive neurodegenerative disorder linked to brain hypomyelination and leukodystrophy. Am. J. Hum. Genet. 83 (2008) 30-42
84. Hansen J.J., et al. Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. Am. J. Hum. Genet. 70 (2002) 1328-1332
85. Spiess C., Meyer A.S., Reissmann S., and Frydman J. Mechanism of the eukaryotic chaperonin: protein folding in the chamber of secrets. Trends Cell Biol. 14 (2004) 598-604
86. Albanese V., Yam A.Y., Baughman J., Parnot C., and Frydman J. Systems analyses reveal two chaperone networks with distinct functions in eukaryotic cells. Cell 124 (2006) 75-88
87. Kim S., Willison K.R., and Horwich A.L. Cystosolic chaperonin subunits have a conserved ATPase domain but diverged polypeptide-binding domains. Trends Biochem. Sci. 19 (1994) 543-548
88. Yam A.Y., Xia Y., Lin H.T., Burlingame A., Gerstein M., and Frydman J. Defining the TRiC/CCT interactome links chaperonin function to stabilization of newly made proteins with complex topologies. Nat. Struct. Mol. Biol. 15 (2008) 1255-1262
89. Thulasiraman V., Yang C.F., and Frydman J. In vivo newly translated polypeptides are sequestered in a protected folding environment. EMBO J. 18 (1999) 85-95
90. Tam S., Geller R., Spiess C., and Frydman J. The chaperonin TRiC controls polyglutamine aggregation and toxicity through subunit-specific interactions. Nat. Cell Biol. 8 (2006) 1155-1162
91. Kitamura A., et al. Cytosolic chaperonin prevents polyglutamine toxicity with altering the aggregation state. Nat. Cell Biol. 8 (2006) 1163-1170
92. Nollen E.A., Garcia S.M., van Haaften G., Kim S., Chavez A., Morimoto R.I., and Plasterk R.H. Genome-wide RNA interference screen identifies previously undescribed regulators of polyglutamine aggregation. Proc. Natl. Acad. Sci. USA 101 (2004) 6403-6408
93. Rommelaere H., De Neve M., Melki R., Vandekerckhove J., and Ampe C. The cytosolic class II chaperonin CCT recognizes delineated hydrophobic sequences in its target proteins. Biochemistry 38 (1999) 3246-3257
94. Camasses A., Bogdanova A., Shevchenko A., and Zachariae W. The CCT chaperonin promotes activation of the anaphase-promoting complex through the generation of functional Cdc20. Mol. Cell 12 (2003) 87-100
95. Feldman D.E., Spiess C., Howard D.E., and Frydman J. Tumorigenic mutations in VHL disrupt folding in vivo by interfering with chaperonin binding. Mol. Cell 12 (2003) 1213-1224
96. Kubota S., Kubota H., and Nagata K. Cytosolic chaperonin protects folding intermediates of Gbeta from aggregation by recognizing hydrophobic beta-strands. Proc. Natl. Acad. Sci. USA 103 (2006) 8360-8365
97. Westerheide S.D., and Morimoto R.I. Heat shock response modulators as therapeutic tools for diseases of protein conformation. J. Biol. Chem. 280 (2005) 33097-33100
98. Sittler A., Lurz R., Lueder G., Priller J., Lehrach H., Hayer-Hartl M.K., Hartl F.U., and Wanker E.E. Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington's disease. Hum. Mol. Genet. 10 (2001) 1307-1315
99. Waza M., et al. 17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration. Nat. Med. 11 (2005) 1088-1095
100. Fujikake N., Nagai Y., Popiel H.A., Okamoto Y., Yamaguchi M., and Toda T. Heat shock transcription factor 1-activating compounds suppress polyglutamine-induced neurodegeneration through induction of multiple molecular chaperones. J. Biol. Chem. 283 (2008) 26188-26197
101. Solit D.B., et al. Phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with metastatic melanoma. Clin. Cancer Res. 14 (2008) 8302-8307
102. Ronnen E.A., Kondagunta G.V., Ishill N., Sweeney S.M., Deluca J.K., Schwartz L., Bacik J., and Motzer R.J. A phase II trial of 17-(Allylamino)-17-demethoxygeldanamycin in patients with papillary and clear cell renal cell carcinoma. Invest. New Drugs 24 (2006) 543-546
103. Ansar S., et al. A non-toxic Hsp90 inhibitor protects neurons from Abeta-induced toxicity. Bioorg. Med. Chem. Lett. 17 (2007) 1984-1990
104. Lavu S., Boss O., Elliott P.J., and Lambert P.D. Sirtuins-novel therapeutic targets to treat age-associated diseases. Nat. Rev. Drug Discov. 7 (2008) 841-853
105. Westerheide S.D., Anckar J., Stevens Jr. S.M., Sistonen L., and Morimoto R.I. Stress-inducible regulation of heat shock factor 1 by the deacetylase SIRT1. Science 323 (2009) 1063-1066
106. Kalmar B., Novoselov S., Gray A., Cheetham M.E., Margulis B., and Greensmith L. Late stage treatment with arimoclomol delays disease progression and prevents protein aggregation in the SOD1 mouse model of ALS. J. Neurochem. 107 (2008) 339-350
107. Westerheide S.D., et al. Celastrols as inducers of the heat shock response and cytoprotection. J. Biol. Chem. 279 (2004) 56053-56060