1932

Abstract

Loss of protein homeostasis (proteostasis) is a common feature of aging and disease that is characterized by the appearance of nonnative protein aggregates in various tissues. Protein aggregation is routinely suppressed by the proteostasis network (PN), a collection of macromolecular machines that operate in diverse ways to maintain proteome integrity across subcellular compartments and between tissues to ensure a healthy life span. Here, we review the composition, function, and organizational properties of the PN in the context of individual cells and entire organisms and discuss the mechanisms by which disruption of the PN, and related stress response pathways, contributes to the initiation and progression of disease. We explore emerging evidence that disease susceptibility arises from early changes in the composition and activity of the PN and propose that a more complete understanding of the temporal and spatial properties of the PN will enhance our ability to develop effective treatments for protein conformational diseases.

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2015-06-02
2024-04-25
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Literature Cited

  1. Powers ET, Morimoto RI, Dillin A, Kelly JW, Balch WE. 1.  2009. Biological and chemical approaches to diseases of proteostasis deficiency. Annu. Rev. Biochem. 78:959–91 [Google Scholar]
  2. Krstic D, Knuesel I. 2.  2013. Deciphering the mechanism underlying late-onset Alzheimer disease. Nat. Rev. Neurol. 9:25–34 [Google Scholar]
  3. Labbadia J, Morimoto RI. 3.  2013. Huntington's disease: underlying molecular mechanisms and emerging concepts. Trends Biochem. Sci. 38:378–85 [Google Scholar]
  4. Robberecht W, Philips T. 4.  2013. The changing scene of amyotrophic lateral sclerosis. Nat. Rev. Neurosci. 14:248–64 [Google Scholar]
  5. Trinh J, Farrer M. 5.  2013. Advances in the genetics of Parkinson disease. Nat. Rev. Neurol. 9:445–54 [Google Scholar]
  6. Chiti F, Dobson CM. 6.  2006. Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem. 75:333–66 [Google Scholar]
  7. Akerfelt M, Morimoto RI, Sistonen L. 7.  2010. Heat shock factors: integrators of cell stress, development and lifespan. Nat. Rev. Mol. Cell Biol. 11:545–55 [Google Scholar]
  8. Walter P, Ron D. 8.  2011. The unfolded protein response: from stress pathway to homeostatic regulation. Science 334:1081–86 [Google Scholar]
  9. Powers ET, Balch WE. 9.  2013. Diversity in the origins of proteostasis networks—a driver for protein function in evolution. Nat. Rev. Mol. Cell Biol. 14:237–48 [Google Scholar]
  10. Haslbeck M, Franzmann T, Weinfurtner D, Buchner J. 10.  2005. Some like it hot: the structure and function of small heat-shock proteins. Nat. Struct. Mol. Biol. 12:842–46 [Google Scholar]
  11. Kim YE, Hipp MS, Bracher A, Hayer-Hartl M, Hartl FU. 11.  2013. Molecular chaperone functions in protein folding and proteostasis. Annu. Rev. Biochem. 82:323–55 [Google Scholar]
  12. Taipale M, Jarosz DF, Lindquist S. 12.  2010. HSP90 at the hub of protein homeostasis: emerging mechanistic insights. Nat. Rev. Mol. Cell Biol. 11:515–28 [Google Scholar]
  13. Kampinga HH, Craig EA. 13.  2010. The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat. Rev. Mol. Cell Biol. 11:579–92 [Google Scholar]
  14. Connell P, Ballinger CA, Jiang J, Wu Y, Thompson LJ. 14.  et al. 2001. The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat. Cell Biol. 3:93–96 [Google Scholar]
  15. Demand J, Alberti S, Patterson C, Hohfeld J. 15.  2001. Cooperation of a ubiquitin domain protein and an E3 ubiquitin ligase during chaperone/proteasome coupling. Curr. Biol. 11:1569–77 [Google Scholar]
  16. Taipale M, Tucker G, Peng J, Krykbaeva I, Lin ZY. 16.  et al. 2014. A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways. Cell 158:434–48 [Google Scholar]
  17. Preissler S, Deuerling E. 17.  2012. Ribosome-associated chaperones as key players in proteostasis. Trends Biochem. Sci. 37:274–83 [Google Scholar]
  18. Rampelt H, Kirstein-Miles J, Nillegoda NB, Chi K, Scholz SR. 18.  et al. 2012. Metazoan Hsp70 machines use Hsp110 to power protein disaggregation. EMBO J. 31:4221–35 [Google Scholar]
  19. Doyle SM, Genest O, Wickner S. 19.  2013. Protein rescue from aggregates by powerful molecular chaperone machines. Nat. Rev. Mol. Cell Biol. 14:617–29 [Google Scholar]
  20. Finley D. 20.  2009. Recognition and processing of ubiquitin–protein conjugates by the proteasome. Annu. Rev. Biochem. 78:477–513 [Google Scholar]
  21. Yang Z, Klionsky DJ. 21.  2010. Mammalian autophagy: core molecular machinery and signaling regulation. Curr. Opin. Cell Biol. 22:124–31 [Google Scholar]
  22. Coux O, Tanaka K, Goldberg AL. 22.  1996. Structure and functions of the 20S and 26S proteasomes. Annu. Rev. Biochem. 65:801–47 [Google Scholar]
  23. Kisselev AF, Akopian TN, Woo KM, Goldberg AL. 23.  1999. The sizes of peptides generated from protein by mammalian 26 and 20 S proteasomes. Implications for understanding the degradative mechanism and antigen presentation. J. Biol. Chem. 274:3363–71 [Google Scholar]
  24. Chau V, Tobias JW, Bachmair A, Marriott D, Ecker DJ. 24.  et al. 1989. A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. Science 243:1576–83 [Google Scholar]
  25. Yao T, Cohen RE. 25.  2002. A cryptic protease couples deubiquitination and degradation by the proteasome. Nature 419:403–7 [Google Scholar]
  26. Verma R, Aravind L, Oania R, McDonald WH, Yates JR 3rd. 26.  et al. 2002. Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome. Science 298:611–15 [Google Scholar]
  27. Hanna J, Hathaway NA, Tone Y, Crosas B, Elsässer S. 27.  et al. 2006. Deubiquitinating enzyme Ubp6 functions noncatalytically to delay proteasomal degradation. Cell 127:99–111 [Google Scholar]
  28. Lam YA, Xu W, DeMartino GN, Cohen RE. 28.  1997. Editing of ubiquitin conjugates by an isopeptidase in the 26S proteasome. Nature 385:737–40 [Google Scholar]
  29. Nakatsukasa K, Kamura T, Brodsky JL. 29.  2014. Recent technical developments in the study of ER-associated degradation. Curr. Opin. Cell Biol. 29C:82–91 [Google Scholar]
  30. Houck SA, Ren HY, Madden VJ, Bonner JN, Conlin MP. 30.  et al. 2014. Quality control autophagy degrades soluble ERAD-resistant conformers of the misfolded membrane protein GnRHR. Mol. Cell 54:166–79 [Google Scholar]
  31. Kaushik S, Cuervo AM. 31.  2012. Chaperone-mediated autophagy: a unique way to enter the lysosome world. Trends Cell Biol. 22:407–17 [Google Scholar]
  32. Haynes CM, Fiorese CJ, Lin YF. 32.  2013. Evaluating and responding to mitochondrial dysfunction: the mitochondrial unfolded-protein response and beyond. Trends Cell Biol. 23:311–18 [Google Scholar]
  33. Zou J, Guo Y, Guettouche T, Smith DF, Voellmy R. 33.  1998. Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1. Cell 94:471–80 [Google Scholar]
  34. Shi Y, Mosser DD, Morimoto RI. 34.  1998. Molecular chaperones as HSF1-specific transcriptional repressors. Genes Dev. 12:654–66 [Google Scholar]
  35. Baler R, Dahl G, Voellmy R. 35.  1993. Activation of human heat shock genes is accompanied by oligomerization, modification, and rapid translocation of heat shock transcription factor HSF1. Mol. Cell. Biol. 13:2486–96 [Google Scholar]
  36. Westerheide SD, Anckar J, Stevens SM Jr, Sistonen L, Morimoto RI. 36.  2009. Stress-inducible regulation of heat shock factor 1 by the deacetylase SIRT1. Science 323:1063–66 [Google Scholar]
  37. Raychaudhuri S, Loew C, Körner R, Pinkert S, Theis M. 37.  et al. 2014. Interplay of acetyltransferase EP300 and the proteasome system in regulating heat shock transcription factor 1. Cell 156:975–85 [Google Scholar]
  38. Shalgi R, Hurt JA, Lindquist S, Burge CB. 38.  2014. Widespread inhibition of posttranscriptional splicing shapes the cellular transcriptome following heat shock. Cell Rep. 7:1362–70 [Google Scholar]
  39. Shalgi R, Hurt JA, Krykbaeva I, Taipale M, Lindquist S, Burge CB. 39.  2013. Widespread regulation of translation by elongation pausing in heat shock. Mol. Cell 49:439–52 [Google Scholar]
  40. Albanese V, Yam AY, Baughman J, Parnot C, Frydman J. 40.  2006. Systems analyses reveal two chaperone networks with distinct functions in eukaryotic cells. Cell 124:75–88 [Google Scholar]
  41. Brandman O, Stewart-Ornstein J, Wong D, Larson A, Williams CC. 41.  et al. 2012. A ribosome-bound quality control complex triggers degradation of nascent peptides and signals translation stress. Cell 151:1042–54 [Google Scholar]
  42. van Oosten–Hawle P, Morimoto RI. 42.  2014. Organismal proteostasis: role of cell-nonautonomous regulation and transcellular chaperone signaling. Genes Dev. 28:1533–43 [Google Scholar]
  43. Prahlad V, Cornelius T, Morimoto RI. 43.  2008. Regulation of the cellular heat shock response in Caenorhabditis elegans by thermosensory neurons. Science 320:811–14 [Google Scholar]
  44. Prahlad V, Morimoto RI. 44.  2011. Neuronal circuitry regulates the response of Caenorhabditis elegans to misfolded proteins. PNAS 108:14204–9 [Google Scholar]
  45. Durieux J, Wolff S, Dillin A. 45.  2011. The cell-non-autonomous nature of electron transport chain–mediated longevity. Cell 144:79–91 [Google Scholar]
  46. Taylor RC, Dillin A. 46.  2013. XBP-1 is a cell-nonautonomous regulator of stress resistance and longevity. Cell 153:1435–47 [Google Scholar]
  47. van Oosten–Hawle P, Porter RS, Morimoto RI. 47.  2013. Regulation of organismal proteostasis by transcellular chaperone signaling. Cell 153:1366–78 [Google Scholar]
  48. Demontis F, Perrimon N. 48.  2010. FOXO/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging. Cell 143:813–25 [Google Scholar]
  49. Shemesh N, Shai N, Ben-Zvi A. 49.  2013. Germline stem cell arrest inhibits the collapse of somatic proteostasis early in Caenorhabditis elegans adulthood. Aging Cell 12:814–22 [Google Scholar]
  50. Vilchez D, Morantte I, Liu Z, Douglas PM, Merkwirth C. 50.  et al. 2012. RPN-6 determines C. elegans longevity under proteotoxic stress conditions. Nature 489:263–68 [Google Scholar]
  51. Ermolaeva MA, Segref A, Dakhovnik A, Ou HL, Schneider JI. 51.  et al. 2013. DNA damage in germ cells induces an innate immune response that triggers systemic stress resistance. Nature 501:416–20 [Google Scholar]
  52. Lapierre LR, Gelino S, Melendez A, Hansen M. 52.  2011. Autophagy and lipid metabolism coordinately modulate life span in germline-less C. elegans. Curr. Biol. 21:1507–14 [Google Scholar]
  53. Vilchez D, Boyer L, Morantte I, Lutz M, Merkwirth C. 53.  et al. 2012. Increased proteasome activity in human embryonic stem cells is regulated by PSMD11. Nature 489:304–8 [Google Scholar]
  54. Tebbenkamp AT, Borchelt DR. 54.  2010. Analysis of chaperone mRNA expression in the adult mouse brain by meta analysis of the Allen Brain Atlas. PLOS ONE 5:e13675 [Google Scholar]
  55. Guisbert E, Czyz DM, Richter K, McMullen PD, Morimoto RI. 55.  2013. Identification of a tissue-selective heat shock response regulatory network. PLOS Genet. 9:e1003466 [Google Scholar]
  56. Batulan Z, Shinder GA, Minotti S, He BP, Doroudchi MM. 56.  et al. 2003. High threshold for induction of the stress response in motor neurons is associated with failure to activate HSF1. J. Neurosci. 23:5789–98 [Google Scholar]
  57. Tagawa K, Marubuchi S, Qi ML, Enokido Y, Tamura T. 57.  et al. 2007. The induction levels of heat shock protein 70 differentiate the vulnerabilities to mutant huntingtin among neuronal subtypes. J. Neurosci. 27:868–80 [Google Scholar]
  58. Tsvetkov AS, Arrasate M, Barmada S, Ando DM, Sharma P. 58.  et al. 2013. Proteostasis of polyglutamine varies among neurons and predicts neurodegeneration. Nat. Chem. Biol. 9:586–92 [Google Scholar]
  59. Knowles TP, Vendruscolo M, Dobson CM. 59.  2014. The amyloid state and its association with protein misfolding diseases. Nat. Rev. Mol. Cell Biol. 15:384–96 [Google Scholar]
  60. Hipp MS, Park SH, Hartl FU. 60.  2014. Proteostasis impairment in protein-misfolding and -aggregation diseases. Trends Cell Biol. 9:506–14 [Google Scholar]
  61. Sontag EM, Vonk WI, Frydman J. 61.  2014. Sorting out the trash: the spatial nature of eukaryotic protein quality control. Curr. Opin. Cell Biol. 26:139–46 [Google Scholar]
  62. Morley JF, Brignull HR, Weyers JJ, Morimoto RI. 62.  2002. The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans. PNAS 99:10417–22 [Google Scholar]
  63. Gidalevitz T, Ben-Zvi A, Ho KH, Brignull HR, Morimoto RI. 63.  2006. Progressive disruption of cellular protein folding in models of polyglutamine diseases. Science 311:1471–74 [Google Scholar]
  64. Hay DG, Sathasivam K, Tobaben S, Stahl B, Marber M. 64.  et al. 2004. 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. 13:1389–405 [Google Scholar]
  65. Kim S, Nollen EA, Kitagawa K, Bindokas VP, Morimoto RI. 65.  2002. Polyglutamine protein aggregates are dynamic. Nat. Cell Biol. 4:826–31 [Google Scholar]
  66. Yamanaka T, Miyazaki H, Oyama F, Kurosawa M, Washizu C. 66.  et al. 2008. Mutant Huntingtin reduces HSP70 expression through the sequestration of NF-Y transcription factor. EMBO J. 27:827–39 [Google Scholar]
  67. Xu G, Stevens SM Jr, Moore BD, McClung S, Borchelt DR. 67.  2013. Cytosolic proteins lose solubility as amyloid deposits in a transgenic mouse model of Alzheimer-type amyloidosis. Hum. Mol. Genet. 22:2765–74 [Google Scholar]
  68. Auluck PK, Chan HY, Trojanowski JQ, Lee VM, Bonini NM. 68.  2002. Chaperone suppression of α-synuclein toxicity in a Drosophila model for Parkinson's disease. Science 295:865–68 [Google Scholar]
  69. Fonte V, Kapulkin WJ, Taft A, Fluet A, Friedman D, Link CD. 69.  2002. Interaction of intracellular β amyloid peptide with chaperone proteins. PNAS 99:9439–44 [Google Scholar]
  70. McLean PJ, Kawamata H, Shariff S, Hewett J, Sharma N. 70.  et al. 2002. TorsinA and heat shock proteins act as molecular chaperones: suppression of α-synuclein aggregation. J. Neurochem. 83:846–54 [Google Scholar]
  71. Chai Y, Koppenhafer SL, Bonini NM, Paulson HL. 71.  1999. Analysis of the role of heat shock protein (Hsp) molecular chaperones in polyglutamine disease. J. Neurosci. 19:10338–47 [Google Scholar]
  72. Yu A, Shibata Y, Shah B, Calamini B, Lo DC, Morimoto RI. 72.  2014. Protein aggregation can inhibit clathrin-mediated endocytosis by chaperone competition. PNAS 111:e1481–90 [Google Scholar]
  73. Gregori L, Fuchs C, Figueiredo-Pereira ME, Van Nostrand WE, Goldgaber D. 73.  1995. Amyloid β-protein inhibits ubiquitin-dependent protein degradation in vitro. J. Biol. Chem. 270:19702–8 [Google Scholar]
  74. Keller JN, Hanni KB, Markesbery WR. 74.  2000. Impaired proteasome function in Alzheimer's disease. J. Neurochem. 75:436–39 [Google Scholar]
  75. Lam YA, Pickart CM, Alban A, Landon M, Jamieson C. 75.  et al. 2000. Inhibition of the ubiquitin–proteasome system in Alzheimer's disease. PNAS 97:9902–6 [Google Scholar]
  76. Cheroni C, Marino M, Tortarolo M, Veglianese P, De Biasi S. 76.  et al. 2009. Functional alterations of the ubiquitin–proteasome system in motor neurons of a mouse model of familial amyotrophic lateral sclerosis. Hum. Mol. Genet. 18:82–96 [Google Scholar]
  77. Matsumoto G, Stojanovic A, Holmberg CI, Kim S, Morimoto RI. 77.  2005. Structural properties and neuronal toxicity of amyotrophic lateral sclerosis–associated Cu/Zn superoxide dismutase 1 aggregates. J. Cell Biol. 171:75–85 [Google Scholar]
  78. McNaught KS, Jenner P. 78.  2001. Proteasomal function is impaired in substantia nigra in Parkinson's disease. Neurosci. Lett. 297:191–94 [Google Scholar]
  79. Um JW, Im E, Lee HJ, Min B, Yoo L. 79.  et al. 2010. Parkin directly modulates 26S proteasome activity. J. Neurosci. 30:11805–14 [Google Scholar]
  80. Holmberg CI, Staniszewski KE, Mensah KN, Matouschek A, Morimoto RI. 80.  2004. Inefficient degradation of truncated polyglutamine proteins by the proteasome. EMBO J. 23:4307–18 [Google Scholar]
  81. Bennett EJ, Shaler TA, Woodman B, Ryu KY, Zaitseva TS. 81.  et al. 2007. Global changes to the ubiquitin system in Huntington's disease. Nature 448:704–8 [Google Scholar]
  82. Hipp MS, Patel CN, Bersuker K, Riley BE, Kaiser SE. 82.  et al. 2012. Indirect inhibition of 26S proteasome activity in a cellular model of Huntington's disease. J. Cell Biol. 196:573–87 [Google Scholar]
  83. Park SH, Kukushkin Y, Gupta R, Chen T, Konagai A. 83.  et al. 2013. PolyQ proteins interfere with nuclear degradation of cytosolic proteins by sequestering the Sis1p chaperone. Cell 154:134–45 [Google Scholar]
  84. Komatsu M, Waguri S, Chiba T, Murata S, Iwata J. 84.  et al. 2006. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441:880–84 [Google Scholar]
  85. Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y. 85.  et al. 2006. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441:885–89 [Google Scholar]
  86. Boland B, Kumar A, Lee S, Platt FM, Wegiel J. 86.  et al. 2008. Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer's disease. J. Neurosci. 28:6926–37 [Google Scholar]
  87. Lee JH, Yu WH, Kumar A, Lee S, Mohan PS. 87.  et al. 2010. Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell 141:1146–58 [Google Scholar]
  88. Winslow AR, Chen CW, Corrochano S, Acevedo-Arozena A, Gordon DE. 88.  et al. 2010. α-Synuclein impairs macroautophagy: implications for Parkinson's disease. J. Cell Biol. 190:1023–37 [Google Scholar]
  89. Cuervo AM, Stefanis L, Fredenburg R, Lansbury PT, Sulzer D. 89.  2004. Impaired degradation of mutant α-synuclein by chaperone-mediated autophagy. Science 305:1292–95 [Google Scholar]
  90. Martinez-Vicente M, Talloczy Z, Kaushik S, Massey AC, Mazzulli J. 90.  et al. 2008. Dopamine-modified α-synuclein blocks chaperone-mediated autophagy. J. Clin. Investig. 118:777–88 [Google Scholar]
  91. Martinez-Vicente M, Talloczy Z, Wong E, Tang G, Koga H. 91.  et al. 2010. Cargo recognition failure is responsible for inefficient autophagy in Huntington's disease. Nat. Neurosci. 13:567–76 [Google Scholar]
  92. Bandyopadhyay U, Nagy M, Fenton WA, Horwich AL. 92.  2014. Absence of lipofuscin in motor neurons of SOD1-linked ALS mice. PNAS 111:11055–60 [Google Scholar]
  93. Chan WM, Tsoi H, Wu CC, Wong CH, Cheng TC. 93.  et al. 2011. Expanded polyglutamine domain possesses nuclear export activity which modulates subcellular localization and toxicity of polyQ disease protein via exportin-1. Hum. Mol. Genet. 20:1738–50 [Google Scholar]
  94. Huang S, Ling JJ, Yang S, Li XJ, Li S. 94.  2011. Neuronal expression of TATA box–binding protein containing expanded polyglutamine in knock-in mice reduces chaperone protein response by impairing the function of nuclear factor Y transcription factor. Brain: J. Neurol. 134:1943–58 [Google Scholar]
  95. Labbadia J, Cunliffe H, Weiss A, Katsyuba E, Sathasivam K. 95.  et al. 2011. Altered chromatin architecture underlies progressive impairment of the heat shock response in mouse models of Huntington disease. J. Clin. Investig. 121:3306–19 [Google Scholar]
  96. Silva-Fernandes A, Duarte-Silva S, Neves-Carvalho A, Amorim M, Soares-Cunha C. 96.  et al. 2014. Chronic treatment with 17-DMAG improves balance and coordination in a new mouse model of Machado–Joseph disease. J. Am. Soc. Exp. Neurother. 11:433–49 [Google Scholar]
  97. Maheshwari M, Bhutani S, Das A, Mukherjee R, Sharma A. 97.  et al. 2014. Dexamethasone induces heat shock response and slows down disease progression in mouse and fly models of Huntington's disease. Hum. Mol. Genet. 23:2737–51 [Google Scholar]
  98. Chafekar SM, Duennwald ML. 98.  2012. Impaired heat shock response in cells expressing full-length polyglutamine-expanded huntingtin. PLOS ONE 7:e37929 [Google Scholar]
  99. Olzscha H, Schermann SM, Woerner AC, Pinkert S, Hecht MH. 99.  et al. 2011. Amyloid-like aggregates sequester numerous metastable proteins with essential cellular functions. Cell 144:67–78 [Google Scholar]
  100. Riva L, Koeva M, Yildirim F, Pirhaji L, Dinesh D. 100.  et al. 2012. Poly-glutamine expanded huntingtin dramatically alters the genome wide binding of HSF1. J. Huntington's Dis. 1:33–45 [Google Scholar]
  101. Hetz C, Mollereau B. 101.  2014. Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases. Nat. Rev. Neurosci. 15:233–49 [Google Scholar]
  102. Gkogkas C, Middleton S, Kremer AM, Wardrope C, Hannah M. 102.  et al. 2008. VAPB interacts with and modulates the activity of ATF6. Hum. Mol. Genet. 17:1517–26 [Google Scholar]
  103. Fernandez-Fernandez MR, Ferrer I, Lucas JJ. 103.  2011. Impaired ATF6α processing, decreased Rheb and neuronal cell cycle re-entry in Huntington's disease. Neurobiol. Dis. 41:23–32 [Google Scholar]
  104. Cicchetti F, Saporta S, Hauser RA, Parent M, Saint-Pierre M. 104.  et al. 2009. Neural transplants in patients with Huntington's disease undergo disease-like neuronal degeneration. PNAS 106:12483–88 [Google Scholar]
  105. Li JY, Englund E, Holton JL, Soulet D, Hagell P. 105.  et al. 2008. Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat. Med. 14:501–3 [Google Scholar]
  106. Hansen C, Angot E, Bergström AL, Steiner JA, Pieri L. 106.  et al. 2011. α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. J. Clin. Investig. 121:715–25 [Google Scholar]
  107. Ren PH, Lauckner JE, Kachirskaia I, Heuser JE, Melki R, Kopito RR. 107.  2009. Cytoplasmic penetration and persistent infection of mammalian cells by polyglutamine aggregates. Nat. Cell Biol. 11:219–25 [Google Scholar]
  108. Pecho-Vrieseling E, Rieker C, Fuchs S, Bleckmann D, Esposito MS. 108.  et al. 2014. Transneuronal propagation of mutant huntingtin contributes to non-cell autonomous pathology in neurons. Nat. Neurosci. 17:1064–72 [Google Scholar]
  109. Nussbaum-Krammer CI, Park KW, Li L, Melki R, Morimoto RI. 109.  2013. Spreading of a prion domain from cell-to-cell by vesicular transport in Caenorhabditis elegans. PLOS Genet. 9:e1003351 [Google Scholar]
  110. Munch C, O'Brien J, Bertolotti A. 110.  2011. Prion-like propagation of mutant superoxide dismutase 1 misfolding in neuronal cells. PNAS 108:3548–53 [Google Scholar]
  111. Carnemolla A, Labbadia JP, Lazell H, Neueder A, Moussaoui S, Bates GP. 111.  2014. Contesting the dogma of an age-related heat shock response impairment: implications for cardiac-specific age-related disorders. Hum. Mol. Genet. 23:3641–56 [Google Scholar]
  112. Blake MJ, Udelsman R, Feulner GJ, Norton DD, Holbrook NJ. 112.  1991. Stress-induced heat shock protein 70 expression in adrenal cortex: an adrenocorticotropic hormone-sensitive, age-dependent response. PNAS 88:9873–77 [Google Scholar]
  113. Brehme M, Voisine C, Rolland T, Wachi S, Soper JH. 113.  et al. 2014. A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease. Cell Rep. 3:1135–50 [Google Scholar]
  114. Ben-Zvi A, Miller EA, Morimoto RI. 114.  2009. Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging. PNAS 106:14914–19 [Google Scholar]
  115. David DC, Ollikainen N, Trinidad JC, Cary MP, Burlingame AL, Kenyon C. 115.  2010. Widespread protein aggregation as an inherent part of aging in C. elegans. PLOS Biol. 8:e1000450 [Google Scholar]
  116. Reis-Rodrigues P, Czerwieniec G, Peters TW, Evani US, Alavez S. 116.  et al. 2012. Proteomic analysis of age-dependent changes in protein solubility identifies genes that modulate lifespan. Aging Cell 11:120–27 [Google Scholar]
  117. Kirstein-Miles J, Morimoto RI. 117.  2013. Ribosome-associated chaperones act as proteostasis sentinels. Cell Cycle 12:2335–36 [Google Scholar]
  118. Xiao X, Zuo X, Davis AA, McMillan DR, Curry BB. 118.  et al. 1999. HSF1 is required for extra-embryonic development, postnatal growth and protection during inflammatory responses in mice. EMBO J. 18:5943–52 [Google Scholar]
  119. Jedlicka P, Mortin MA, Wu C. 119.  1997. Multiple functions of Drosophila heat shock transcription factor in vivo. EMBO J. 16:2452–62 [Google Scholar]
  120. Sorger PK, Pelham HR. 120.  1988. Yeast heat shock factor is an essential DNA-binding protein that exhibits temperature-dependent phosphorylation. Cell 54:855–64 [Google Scholar]
  121. Walker GA, Thompson FJ, Brawley A, Scanlon T, Devaney E. 121.  2003. Heat shock factor functions at the convergence of the stress response and developmental pathways in Caenorhabditis elegans. FASEB J. 17:1960–62 [Google Scholar]
  122. Dai C, Whitesell L, Rogers AB, Lindquist S. 122.  2007. Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis. Cell 130:1005–18 [Google Scholar]
  123. Pappas C, Hyde D, Bowler K, Loeschcke V, Sørensen JG. 123.  2007. Post-eclosion decline in ‘knock-down’ thermal resistance and reduced effect of heat hardening in Drosophila melanogaster. Comp. Biochem. Physiol. A 146:355–59 [Google Scholar]
  124. Cohen E, Bieschke J, Perciavalle RM, Kelly JW, Dillin A. 124.  2006. Opposing activities protect against age-onset proteotoxicity. Science 313:1604–10 [Google Scholar]
  125. Cohen E, Du D, Joyce D, Kapernick EA, Volovik Y. 125.  et al. 2010. Temporal requirements of insulin/IGF-1 signaling for proteotoxicity protection. Aging Cell 9:126–34 [Google Scholar]
  126. Volovik Y, Maman M, Dubnikov T, Bejerano-Sagie M, Joyce D. 126.  et al. 2012. Temporal requirements of heat shock factor 1 for longevity assurance. Aging Cell 11:491–99 [Google Scholar]
  127. Dillin A, Crawford DK, Kenyon C. 127.  2002. Timing requirements for insulin/IGF-1 signaling in C. elegans. Science 298:830–34 [Google Scholar]
  128. Hamer G, Matilainen O, Holmberg CI. 128.  2010. A photoconvertible reporter of the ubiquitin–proteasome system in vivo. Nat. Methods 7:473–78 [Google Scholar]
  129. Liu G, Rogers J, Murphy CT, Rongo C. 129.  2011. EGF signalling activates the ubiquitin–proteasome system to modulate C. elegans lifespan. EMBO J. 30:2990–3003 [Google Scholar]
  130. Keller JN, Huang FF, Markesbery WR. 130.  2000. Decreased levels of proteasome activity and proteasome expression in aging spinal cord. Neuroscience 98:149–56 [Google Scholar]
  131. Tonoki A, Kuranaga E, Tomioka T, Hamazaki J, Murata S. 131.  et al. 2009. Genetic evidence linking age-dependent attenuation of the 26S proteasome with the aging process. Mol. Cell. Biol. 29:1095–106 [Google Scholar]
  132. Sittler A, Lurz R, Lueder G, Priller J, Lehrach H. 132.  et al. 2001. Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington's disease. Hum. Mol. Genet. 10:1307–15 [Google Scholar]
  133. Waza M, Adachi H, Katsuno M, Minamiyama M, Sang C. 133.  et al. 2005. 17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration. Nat. Med. 11:1088–95 [Google Scholar]
  134. Fujikake N, Nagai Y, Popiel HA, Okamoto Y, Yamaguchi M, Toda T. 134.  2008. Heat shock transcription factor 1–activating compounds suppress polyglutamine-induced neurodegeneration through induction of multiple molecular chaperones. J. Biol. Chem. 283:26188–97 [Google Scholar]
  135. Auluck PK, Bonini NM. 135.  2002. Pharmacological prevention of Parkinson disease in Drosophila. Nat. Med. 8:1185–86 [Google Scholar]
  136. Calamini B, Silva MC, Madoux F, Hutt DM, Khanna S. 136.  et al. 2012. Small-molecule proteostasis regulators for protein conformational diseases. Nat. Chem. Biol. 8:185–96 [Google Scholar]
  137. Neef DW, Turski ML, Thiele DJ. 137.  2010. Modulation of heat shock transcription factor 1 as a therapeutic target for small molecule intervention in neurodegenerative disease. PLOS Biol. 8:e1000291 [Google Scholar]
  138. Neef DW, Jaeger AM, Gomez-Pastor R, Willmund F, Frydman J, Thiele D. 138.  2014. A direct regulatory interaction between chaperonin TRiC and stress-responsive transcription factor HSF1. Cell Rep. 3:955–66 [Google Scholar]
  139. Roth DM, Hutt DM, Tong J, Bouchecareilh M, Wang N. 139.  et al. 2014. Modulation of the maladaptive stress response to manage diseases of protein folding. PLOS Biol. 11:e1001998 [Google Scholar]
  140. Ravikumar B, Duden R, Rubinsztein DC. 140.  2002. Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum. Mol. Genet. 11:1107–17 [Google Scholar]
  141. Ravikumar B, Vacher C, Berger Z, Davies JE, Luo S. 141.  et al. 2004. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat. Genet. 36:585–95 [Google Scholar]
  142. Berger Z, Ravikumar B, Menzies FM, Oroz LG, Underwood BR. 142.  et al. 2006. Rapamycin alleviates toxicity of different aggregate-prone proteins. Hum. Mol. Genet. 15:433–42 [Google Scholar]
  143. Menzies FM, Huebener J, Renna M, Bonin M, Riess O, Rubinsztein DC. 143.  2010. Autophagy induction reduces mutant ataxin-3 levels and toxicity in a mouse model of spinocerebellar ataxia type 3. Brain: J. Neurol. 133:93–104 [Google Scholar]
  144. Tsvetkov AS, Miller J, Arrasate M, Wong JS, Pleiss MA, Finkbeiner S. 144.  2010. A small-molecule scaffold induces autophagy in primary neurons and protects against toxicity in a Huntington disease model. PNAS 107:16982–87 [Google Scholar]
  145. Barmada SJ, Serio A, Arjun A, Bilican B, Daub A. 145.  et al. 2014. Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models. Nat. Chem. Biol. 10:677–85 [Google Scholar]
  146. Sarkar S, Perlstein EO, Imarisio S, Pineau S, Cordenier A. 146.  et al. 2007. Small molecules enhance autophagy and reduce toxicity in Huntington's disease models. Nat. Chem. Biol. 3:331–38 [Google Scholar]
  147. Lee BH, Lee MJ, Park S, Oh DC, Elsässer S. 147.  et al. 2010. Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature 467:179–84 [Google Scholar]
  148. Smith CD, Carney JM, Starke-Reed PE, Oliver CN, Stadtman ER. 148.  et al. 1991. Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. PNAS 88:10540–43 [Google Scholar]
  149. Sykiotis GP, Bohmann D. 149.  2010. Stress-activated cap'n'collar transcription factors in aging and human disease. Sci. Signal. 3re3
  150. Jin YN, Yu YV, Gundemir S, Jo C, Cui M. 150.  et al. 2013. Impaired mitochondrial dynamics and Nrf2 signaling contribute to compromised responses to oxidative stress in striatal cells expressing full-length mutant huntingtin. PLOS ONE 8:e57932 [Google Scholar]
  151. Kirby J, Halligan E, Baptista MJ, Allen S, Heath PR. 151.  et al. 2005. Mutant SOD1 alters the motor neuronal transcriptome: implications for familial ALS. Brain: J. Neurol. 128:1686–706 [Google Scholar]
  152. Kanninen K, Malm TM, Jyrkkänen HK, Goldsteins G, Keksa-Goldsteine V. 152.  et al. 2008. Nuclear factor erythroid 2–related factor 2 protects against β amyloid. Mol. Cell. Neurosci. 39:302–13 [Google Scholar]
  153. Tsakiri EN, Sykiotis GP, Papassideri IS, Gorgoulis VG, Bohmann D, Trougakos IP. 153.  2013. Differential regulation of proteasome functionality in reproductive versus somatic tissues of Drosophila during aging or oxidative stress. FASEB J. 27:2407–20 [Google Scholar]
  154. Rahman MM, Sykiotis GP, Nishimura M, Bodmer R, Bohmann D. 154.  2013. Declining signal dependence of Nrf2-MafS-regulated gene expression correlates with aging phenotypes. Aging Cell 12:554–62 [Google Scholar]
  155. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P. 155.  et al. 1993. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59–62 [Google Scholar]
  156. Deng HX, Chen W, Hong ST, Boycott KM, Gorrie GH. 156.  et al. 2011. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature 477:211–15 [Google Scholar]
  157. Litt M, Kramer P, LaMorticella DM, Murphey W, Lovrien EW, Weleber RG. 157.  1998. Autosomal dominant congenital cataract associated with a missense mutation in the human α crystallin gene CRYAA. Hum. Mol. Genet. 7:471–74 [Google Scholar]
  158. Hansen JJ, Durr A, Cournu-Rebeix I, Georgopoulos C, Ang D. 158.  et al. 2002. Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. Am. J. Hum. Genet. 70:1328–32 [Google Scholar]
  159. Takiyama Y, Nishizawa M, Tanaka H, Kawashima S, Sakamoto H. 159.  et al. 1993. The gene for Machado–Joseph disease maps to human chromosome 14q. Nat. Genet. 4:300–4 [Google Scholar]
  160. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y. 160.  et al. 1998. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392:605–8 [Google Scholar]
  161. Rajasekaran NS, Connell P, Christians ES, Yan LJ, Taylor RP. 161.  et al. 2007. Human αB-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Cell 130:427–39 [Google Scholar]
  162. Engert JC, Bérubé P, Mercier J, Doré C, Lepage P. 162.  et al. 2000. ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF. Nat. Genet. 24:120–25 [Google Scholar]
  163. Evgrafov OV, Mersiyanova I, Irobi J, Van Den Bosch L, Dierick I. 163.  et al. 2004. Mutant small heat-shock protein 27 causes axonal Charcot–Marie–Tooth disease and distal hereditary motor neuropathy. Nat. Genet. 36:602–6 [Google Scholar]
  164. Watts GD, Wymer J, Kovach MJ, Mehta SG, Mumm S. 164.  et al. 2004. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nat. Genet. 36:377–81 [Google Scholar]
  165. Senderek J, Krieger M, Stendel C, Bergmann C, Moser M. 165.  et al. 2005. Mutations in SIL1 cause Marinesco–Sjögren syndrome, a cerebellar ataxia with cataract and myopathy. Nat. Genet. 37:1312–14 [Google Scholar]
  166. Anttonen AK, Mahjneh I, Hämäläinen RH, Lagier-Tourenne C, Kopra O. 166.  et al. 2005. The gene disrupted in Marinesco–Sjögren syndrome encodes SIL1, an HSPA5 cochaperone. Nat. Genet. 37:1309–11 [Google Scholar]
  167. Tang BS, Zhao GH, Luo W, Xia K, Cai F. 167.  et al. 2005. Small heat-shock protein 22 mutated in autosomal dominant Charcot–Marie–Tooth disease type 2L. Hum. Genet. 116:222–24 [Google Scholar]
  168. Davey KM, Parboosingh JS, McLeod DR, Chan A, Casey R. 168.  et al. 2006. Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome–like condition. J. Med. Genet. 43:385–93 [Google Scholar]
  169. Burbulla LF, Schelling C, Kato H, Rapaport D, Woitalla D. 169.  et al. 2010. Dissecting the role of the mitochondrial chaperone mortalin in Parkinson's disease: functional impact of disease-related variants on mitochondrial homeostasis. Hum. Mol. Genet. 19:4437–52 [Google Scholar]
  170. He M, Guo H, Yang X, Zhou L, Zhang X. 170.  et al. 2010. Genetic variations in HSPA8 gene associated with coronary heart disease risk in a Chinese population. PLOS ONE 5:e9684 [Google Scholar]
  171. Arima K, Kinoshita A, Mishima H, Kanazawa N, Kaneko T. 171.  et al. 2011. Proteasome assembly defect due to a proteasome subunit β type 8 (PSMB8) mutation causes the autoinflammatory disorder, Nakajo–Nishimura syndrome. PNAS 108:14914–19 [Google Scholar]
  172. Blumen SC, Astord S, Robin V, Vignaud L, Toumi N. 172.  et al. 2012. A rare recessive distal hereditary motor neuropathy with HSJ1 chaperone mutation. Ann. Neurol. 71:509–19 [Google Scholar]
  173. Edvardson S, Cinnamon Y, Ta-Shma A, Shaag A, Yim YI. 173.  et al. 2012. A deleterious mutation in DNAJC6 encoding the neuronal-specific clathrin-uncoating co-chaperone auxilin, is associated with juvenile parkinsonism. PLOS ONE 7:e36458 [Google Scholar]
  174. Harms MB, Sommerville RB, Allred P, Bell S, Ma D. 174.  et al. 2012. Exome sequencing reveals DNAJB6 mutations in dominantly inherited myopathy. Ann. Neurol. 71:407–16 [Google Scholar]
  175. Teyssou E, Takeda T, Lebon V, Boillée S, Doukouré B. 175.  et al. 2013. Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: genetics and neuropathology. Acta Neuropathol. 125:511–22 [Google Scholar]
  176. Vilarino-Guell C, Rajput A, Milnerwood AJ, Shah B, Szu-Tu C. 176.  et al. 2014. DNAJC13 mutations in Parkinson disease. Hum. Mol. Genet. 23:1794–801 [Google Scholar]
  177. Kwok CT, Morris AG, Frampton J, Smith B, Shaw CE, de Belleroche J. 177.  2013. Association studies indicate that protein disulfide isomerase is a risk factor in amyotrophic lateral sclerosis. Free Radic. Biol. Med. 58:81–86 [Google Scholar]
  178. Kishino T, Lalande M, Wagstaff J. 178.  1997. UBE3A/E6-AP mutations cause Angelman syndrome. Nat. Genet. 15:70–73 [Google Scholar]
  179. Kieran D, Kalmar B, Dick JR, Riddoch-Contreras J, Burnstock G, Greensmith L. 179.  2004. Treatment with arimoclomol, a coinducer of heat shock proteins, delays disease progression in ALS mice. Nat. Med. 10:402–5 [Google Scholar]
  180. Haldimann P, Muriset M, Vigh L, Goloubinoff P. 180.  2011. The novel hydroxylamine derivative NG-094 suppresses polyglutamine protein toxicity in Caenorhabditis elegans. J. Biol. Chem. 286:18784–94 [Google Scholar]
  181. Katsuno M, Sang C, Adachi H, Minamiyama M, Waza M. 181.  et al. 2005. Pharmacological induction of heat-shock proteins alleviates polyglutamine-mediated motor neuron disease. PNAS 102:16801–6 [Google Scholar]
  182. Williams A, Sarkar S, Cuddon P, Ttofi EK, Saiki S. 182.  et al. 2008. Novel targets for Huntington's disease in an mTOR-independent autophagy pathway. Nat. Chem. Biol. 4:295–305 [Google Scholar]
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