The many faces of autophagy dysfunction in Huntington's disease: From mechanism to therapy

Drug Discovery Today

Volumn 19, Issue 7, 2014, Pages 963-971

  Cortes, Constanza J ^a,b,c,d,e   La Spada, Albert R ^a,b,c,d,e,f  

^a UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f RADY CHILDREN'S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HUNTINGTIN; POLYGLUTAMINE; HTT PROTEIN, HUMAN; NERVE PROTEIN; RAPAMYCIN; TEMSIROLIMUS; TREHALOSE;

ACETYLATION; AUTOPHAGY; BRAIN BIOPSY; BRAIN CELL; BRAIN DEVELOPMENT; CELL DAMAGE; CELL PROLIFERATION; CELL SURVIVAL; CHAPERONE-MEDIATED AUTOPHAGY; CORPUS STRIATUM; DEGENERATIVE DISEASE; ENDOPLASMIC RETICULUM STRESS; ENDOSOME; GOLGI COMPLEX; HUMAN; HUNTINGTON CHOREA; LYSOSOME; MACROAUTOPHAGY; MOTOR PERFORMANCE; MULTIVESICULAR BODY; NONHUMAN; OXIDATIVE STRESS; PROTEIN AGGREGATION; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN HOMEOSTASIS; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; SUMOYLATION; UBIQUITINATION; UNFOLDED PROTEIN RESPONSE; UPREGULATION; ANALOGS AND DERIVATIVES; ANIMAL; DRUG EFFECTS; HUNTINGTON DISEASE; PATHOPHYSIOLOGY; PHYSIOLOGY;

ANIMALS; AUTOPHAGY; ENDOPLASMIC RETICULUM STRESS; HUMANS; HUNTINGTON DISEASE; NERVE TISSUE PROTEINS; SIROLIMUS; TREHALOSE;

EID: 84903770556     PISSN: 13596446     EISSN: 18785832     Source Type: Journal    
DOI: 10.1016/j.drudis.2014.02.014     Document Type: Review

References (55)

1. E. Wong, and A.M. Cuervo Autophagy gone awry in neurodegenerative diseases Nat. Neurosci. 13 2010 805 811
2. T. Hara et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice Nature 441 2006 885 889
3. M. Komatsu et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice Nature 441 2006 880 884
4. E. Sapp et al. Huntingtin localization in brains of normal and Huntington's disease patients Ann. Neurol. 42 1997 604 612 (Pubitemid 27439023)
5. M. DiFiglia et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain Science 277 1997 1990 1993
6. S. Zeitlin et al. Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington's disease gene homologue Nat. Genet. 11 1995 155 163
7. I. Sanchez et al. Pivotal role of oligomerization in expanded polyglutamine neurodegenerative disorders Nature 421 2003 373 379 (Pubitemid 36157935)
8. N.F. Bence et al. Impairment of the ubiquitin-proteasome system by protein aggregation Science 292 2001 1552 1555 (Pubitemid 32493425)
9. M.S. Hipp et al. Indirect inhibition of 26S proteasome activity in a cellular model of Huntington's disease J. Cell Biol. 196 2012 573 587
10. K.B. Kegel et al. Huntingtin expression stimulates endosomal-lysosomal activity, endosome tubulation, and autophagy J. Neurosci. 20 2000 7268 7278
11. T. Tsunemi et al. PGC-1alpha rescues Huntington's disease proteotoxicity by preventing oxidative stress and promoting TFEB function Sci. Transl. Med. 4 2012 142ra197
12. S.H. Park et al. PolyQ proteins interfere with nuclear degradation of cytosolic proteins by sequestering the Sis1p chaperone Cell 154 2013 134 145
13. W.X. Ding, and X.M. Yin Sorting, recognition and activation of the misfolded protein degradation pathways through macroautophagy and the proteasome Autophagy 4 2008 141 150
14. U.B. Pandey et al. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS Nature 447 2007 859 863 (Pubitemid 46920134)
15. B. Ravikumar et al. Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy Hum. Mol. Genet. 11 2002 1107 1117 (Pubitemid 34521091)
16. A. Terman et al. Mitochondrial turnover and aging of long-lived postmitotic cells: the mitochondrial-lysosomal axis theory of aging Antioxid. Redox Signal. 12 2010 503 535
17. I. Tellez-Nagel et al. Studies on brain biopsies of patients with Huntington's chorea J. Neuropathol. Exp. Neurol. 33 1974 308 332
18. M. Martinez-Vicente et al. Cargo recognition failure is responsible for inefficient autophagy in Huntington's disease Nat. Neurosci. 13 2010 567 576
19. H. Lee et al. IRE1 plays an essential role in ER stress-mediated aggregation of mutant huntingtin via the inhibition of autophagy flux Hum. Mol. Genet. 21 2012 101 114
20. B. Ravikumar et al. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease Nat. Genet. 36 2004 585 595 (Pubitemid 38715985)
21. R.S. Atwal et al. Huntingtin has a membrane association signal that can modulate huntingtin aggregation, nuclear entry and toxicity Hum. Mol. Genet. 16 2007 2600 2615 (Pubitemid 47617727)
22. S. Zheng et al. Deletion of the huntingtin polyglutamine stretch enhances neuronal autophagy and longevity in mice PLoS Genet. 6 2010 e1000838
23. R.S. Atwal, and R. Truant A stress sensitive ER membrane-association domain in Huntingtin protein defines a potential role for Huntingtin in the regulation of autophagy Autophagy 4 2008 91 93
24. J.S. Steffan Does Huntingtin play a role in selective macroautophagy? Cell Cycle 9 2010 3401 3413
25. M. Shibata et al. Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1 J. Biol. Chem. 281 2006 14474 14485 (Pubitemid 43848378)
26. S. Kaushik et al. Constitutive activation of chaperone-mediated autophagy in cells with impaired macroautophagy Mol. Biol. Cell 19 2008 2179 2192
27. P. Weydt et al. The gene coding for PGC-1alpha modifies age at onset in Huntington's disease Mol. Neurodegener. 4 2009 3
28. L. Cui et al. Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration Cell 127 2006 59 69 (Pubitemid 44466642)
29. S. Metzger et al. Age at onset in Huntington's disease is modified by the autophagy pathway: implication of the V471A polymorphism in Atg7 Hum. Genet. 128 2010 453 459
30. H. Jeong et al. Acetylation targets mutant huntingtin to autophagosomes for degradation Cell 137 2009 60 72
31. L.M. Thompson et al. IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome J. Cell Biol. 187 2009 1083 1099
32. X. Gu et al. Serines 13 and 16 are critical determinants of full-length human mutant huntingtin induced disease pathogenesis in HD mice Neuron 64 2009 828 840
33. E. Hockly et al. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease Proc. Natl. Acad. Sci. U. S. A. 100 2003 2041 2046 (Pubitemid 36254570)
34. A. Banreti et al. The emerging role of acetylation in the regulation of autophagy Autophagy 9 2013 819 829
35. J.S. Steffan et al. SUMO modification of Huntingtin and Huntington's disease pathology Science 304 2004 100 104 (Pubitemid 38451465)
36. A.M. Cuervo Chaperone-mediated autophagy: selectivity pays off Trends Endocrinol. Metab. 21 2010 142 150
37. L. Qi et al. The role of chaperone-mediated autophagy in huntingtin degradation PLoS ONE 7 2012 e46834
38. H. Koga et al. Constitutive upregulation of chaperone-mediated autophagy in Huntington's disease J. Neurosci. 31 2011 18492 18505
39. P.O. Bauer et al. Harnessing chaperone-mediated autophagy for the selective degradation of mutant huntingtin protein Nat. Biotechnol. 28 2010 256 263
40. J. Wu, and R.J. Kaufman From acute ER stress to physiological roles of the Unfolded Protein Response Cell Death Differ. 13 2006 374 384
41. S. Bernales et al. Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response PLoS Biol. 4 2006 e423
42. J.M. Garcia-Martinez et al. BH3-only proteins Bid and Bim(EL) are differentially involved in neuronal dysfunction in mouse models of Huntington's disease J. Neurosci. Res. 85 2007 2756 2769 (Pubitemid 47344575)
43. A. Carnemolla et al. Rrs1 is involved in endoplasmic reticulum stress response in Huntington disease J. Biol. Chem. 284 2009 18167 18173
44. K. Omi et al. siRNA-mediated inhibition of endogenous Huntington disease gene expression induces an aberrant configuration of the ER network in vitro Biochem. Biophys. Res. Commun. 338 2005 1229 1235 (Pubitemid 41597768)
45. D. del Toro et al. Mutant huntingtin impairs post-Golgi trafficking to lysosomes by delocalizing optineurin/Rab8 complex from the Golgi apparatus Mol. Biol. Cell 20 2009 1478 1492
46. M.M. Zeron et al. Increased sensitivity to N-methyl-d-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington's disease Neuron 33 2002 849 860 (Pubitemid 34246352)
47. R.L. Vidal et al. Targeting the UPR transcription factor XBP1 protects against Huntington's disease through the regulation of FoxO1 and autophagy Hum. Mol. Genet. 21 2012 2245 2262
48. M.L. Duennwald, and S. Lindquist Impaired ERAD and ER stress are early and specific events in polyglutamine toxicity Genes Dev. 22 2008 3308 3319
49. H. Yang et al. Huntingtin interacts with the cue domain of gp78 and inhibits gp78 binding to ubiquitin and p97/VCP PLoS ONE 5 2010 e8905
50. B.P. Culver et al. Proteomic analysis of wild-type and mutant huntingtin-associated proteins in mouse brains identifies unique interactions and involvement in protein synthesis J. Biol. Chem. 287 2012 21599 21614
51. M. Sadagurski et al. IRS2 increases mitochondrial dysfunction and oxidative stress in a mouse model of Huntington disease J. Clin. Invest. 121 2011 4070 4081
52. M. Tanaka et al. Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease Nat. Med. 10 2004 148 154 (Pubitemid 38524884)
53. C. Rose et al. Rilmenidine attenuates toxicity of polyglutamine expansions in a mouse model of Huntington's disease Hum. Mol. Genet. 19 2010 2144 2153
54. H. Jia et al. Selective histone deacetylase (HDAC) inhibition imparts beneficial effects in Huntington's disease mice: implications for the ubiquitin-proteasomal and autophagy systems Hum. Mol. Genet. 21 2012 5280 5293
55. E.A. Thomas et al. The HDAC inhibitor 4b ameliorates the disease phenotype and transcriptional abnormalities in Huntington's disease transgenic mice Proc. Natl. Acad. Sci. U. S. A. 105 2008 15564 15569