Autophagy and misfolded proteins in neurodegeneration

Experimental Neurology

Volumn 238, Issue 1, 2012, Pages 22-28

  Metcalf, Daniel J ^a   García Arencibia, Moisés ^a   Hochfeld, Warren E ^a   Rubinsztein, David C ^a  

^a ADDENBROOKE S HOSPITAL   (United Kingdom)

Author keywords

Autophagy; Huntington's disease; Neurodegeneration

Indexed keywords

AMIODARONE; ANTIOXIDANT; ATAXIN 3; BECLIN 1; CYCLIC AMP; HUNTINGTIN; LOPERAMIDE; LYSOSOME ENZYME; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MINOXIDIL; PHOSPHATIDYLINOSITOL 3 KINASE; RAB PROTEIN; RAPAMYCIN; STAUROSPORINE; SUPEROXIDE DISMUTASE; UBIQUITIN PROTEIN LIGASE; VERAPAMIL;

AUTOLYSOSOME; AUTOPHAGOSOME; AUTOPHAGY; BRAIN NERVE CELL; CELL FUSION; CELL MATURATION; CELL MEMBRANE; CELL PROTECTION; CYTOPLASM; DEGENERATIVE DISEASE; DIFFERENTIAL DIAGNOSIS; GENETIC ANALYSIS; HUMAN; INTRACELLULAR SIGNALING; LIPID DEGRADATION; NERVE DEGENERATION; NONHUMAN; ONSET AGE; PHARMACOLOGICAL STIMULATION; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN INDUCTION; PROTEIN METABOLISM; PROTEIN TRANSPORT; REVIEW; UPREGULATION;

ANIMALS; ANTIOXIDANTS; AUTOPHAGY; HUMANS; LYSOSOMES; NEURODEGENERATIVE DISEASES; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN FOLDING; PROTEOSTASIS DEFICIENCIES; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES;

EID: 84866550924     PISSN: 00144886     EISSN: 10902430     Source Type: Journal    
DOI: 10.1016/j.expneurol.2010.11.003     Document Type: Review

References (92)

1. Aguado C., Sarkar S., Korolchuk V.I., Criado O., Vernia S., Boya P., Sanz P., de Cordoba S.R., Knecht E., Rubinsztein D.C. Laforin, the most common protein mutated in Lafora disease, regulates autophagy. Hum. Mol. Genet. 2010, 19:2867-2876.
2. Atlashkin V., Kreykenbohm V., Eskelinen E.L., Wenzel D., Fayyazi A., Fischer von Mollard G. Deletion of the SNARE vti1b in mice results in the loss of a single SNARE partner, syntaxin 8. Mol. Cell. Biol. 2003, 23:5198-5207.
3. Berger Z., Ravikumar B., Menzies F.M., Oroz L.G., Underwood B.R., Pangalos M.N., Schmitt I., Wullner U., Evert B.O., O'Kane C.J., Rubinsztein D.C. Rapamycin alleviates toxicity of different aggregate-prone proteins. Hum. Mol. Genet. 2006, 15:433-442.
4. Cao Y., Klionsky D.J. Physiological functions of Atg6/Beclin 1: a unique autophagy-related protein. Cell Res. 2007, 17:839-849.
5. Cataldo A.M., Peterhoff C.M., Schmidt S.D., Terio N.B., Duff K., Beard M., Mathews P.M., Nixon R.A. Presenilin mutations in familial Alzheimer disease and transgenic mouse models accelerate neuronal lysosomal pathology. J. Neuropathol. Exp. Neurol. 2004, 63:821-830.
6. Chan E.Y., Longatti A., McKnight N.C., Tooze S.A. Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism. Mol. Cell. Biol. 2009, 29:157-171.
7. Christoforidis S., Miaczynska M., Ashman K., Wilm M., Zhao L., Yip S.C., Waterfield M.D., Backer J.M., Zerial M. Phosphatidylinositol-3-OH kinases are Rab5 effectors. Nat. Cell Biol. 1999, 1:249-252.
8. Criollo A., Maiuri M.C., Tasdemir E., Vitale I., Fiebig A.A., Andrews D., Molgo J., Diaz J., Lavandero S., Harper F., Pierron G., di Stefano D., Rizzuto R., Szabadkai G., Kroemer G. Regulation of autophagy by the inositol trisphosphate receptor. Cell Death Differ. 2007, 14:1029-1039.
9. Filimonenko M., Stuffers S., Raiborg C., Yamamoto A., Malerod L., Fisher E.M., Isaacs A., Brech A., Stenmark H., Simonsen A. Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. J. Cell Biol. 2007, 179:485-500.
10. Fukuda T., Roberts A., Ahearn M., Zaal K., Ralston E., Plotz P.H., Raben N. Autophagy and lysosomes in Pompe disease. Autophagy 2006, 2:318-320.
11. Furuta N., Fujita N., Noda T., Yoshimori T., Amano A. Combinational soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins VAMP8 and Vti1b mediate fusion of antimicrobial and canonical autophagosomes with lysosomes. Mol. Cell. Biol. 2010, 21:1001-1010.
12. Futerman A.H., van Meer G. The cell biology of lysosomal storage disorders. Nat. Rev. Mol. Cell Biol. 2004, 5:554-565.
13. Gutierrez M.G., Munafo D.B., Beron W., Colombo M.I. Rab7 is required for the normal progression of the autophagic pathway in mammalian cells. J. Cell Sci. 2004, 117:2687-2697.
14. Hailey D.W., Rambold A.S., Satpute-Krishnan P., Mitra K., Sougrat R., Kim P.K., Lippincott-Schwartz J. Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 2010, 141:656-667.
15. Hamasaki M., Yoshimori T. Where do they come from? Insights into autophagosome formation. FEBS Lett. 2010, 584:1296-1301.
16. Hara T., Nakamura K., Matsui M., Yamamoto A., Nakahara Y., Suzuki-Migishima R., Yokoyama M., Mishima K., Saito I., Okano H., Mizushima N. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 2006, 441:885-889.
17. Hayashi-Nishino M., Fujita N., Noda T., Yamaguchi A., Yoshimori T., Yamamoto A. A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation. Nat. Cell Biol. 2009, 11:1433-1437.
18. Hosokawa N., Hara T., Kaizuka T., Kishi C., Takamura A., Miura Y., Iemura S., Natsume T., Takehana K., Yamada N., Guan J.L., Oshiro N., Mizushima N. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol. Biol. Cell 2009, 20:1981-1991.
19. Imarisio S., Carmichael J., Korolchuk V., Chen C.W., Saiki S., Rose C., Krishna G., Davies J.E., Ttofi E., Underwood B.R., Rubinsztein D.C. Huntington's disease: from pathology and genetics to potential therapies. Biochem. J. 2008, 412:191-209.
20. Jager S., Bucci C., Tanida I., Ueno T., Kominami E., Saftig P., Eskelinen E.L. Role for Rab7 in maturation of late autophagic vacuoles. J. Cell Sci. 2004, 117:4837-4848.
21. Jahreiss L., Menzies F.M., Rubinsztein D.C. The itinerary of autophagosomes: from peripheral formation to kiss-and-run fusion with lysosomes. Traffic 2008, 9:574-587.
22. Jung C.H., Jun C.B., Ro S.H., Kim Y.M., Otto N.M., Cao J., Kundu M., Kim D.H. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol. Biol. Cell 2009, 20:1992-2003.
23. Jung C.H., Ro S.H., Cao J., Otto N.M., Kim D.H. mTOR regulation of autophagy. FEBS Lett. 2010, 584:1287-1295.
24. Kim P.K., Hailey D.W., Mullen R.T., Lippincott-Schwartz J. Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes. Proc. Natl Acad. Sci. USA 2008, 105:20567-20574.
25. Kimura S., Noda T., Yoshimori T. Dynein-dependent movement of autophagosomes mediates efficient encounters with lysosomes. Cell Struct. Funct. 2008, 33:109-122.
26. Kirkin V., McEwan D.G., Novak I., Dikic I. A role for ubiquitin in selective autophagy. Mol. Cell 2009, 34:259-269.
27. Klionsky D.J., Emr S.D. Autophagy as a regulated pathway of cellular degradation. Science 2000, 290:1717-1721.
28. Kochl R., Hu X.W., Chan E.Y., Tooze S.A. Microtubules facilitate autophagosome formation and fusion of autophagosomes with endosomes. Traffic 2006, 7:129-145.
29. Koike M., Shibata M., Waguri S., Yoshimura K., Tanida I., Kominami E., Gotow T., Peters C., von Figura K., Mizushima N., Saftig P., Uchiyama Y. Participation of autophagy in storage of lysosomes in neurons from mouse models of neuronal ceroid-lipofuscinoses (Batten disease). Am. J. Pathol. 2005, 167:1713-1728.
30. Komatsu M., Waguri S., Chiba T., Murata S., Iwata J., Tanida I., Ueno T., Koike M., Uchiyama Y., Kominami E., Tanaka K. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 2006, 441:880-884.
31. Korolchuk V.I., Mansilla A., Menzies F.M., Rubinsztein D.C. Autophagy inhibition compromises degradation of ubiquitin-proteasome pathway substrates. Mol. Cell 2009, 33:517-527.
32. Kraft C., Reggiori F., Peter M. Selective types of autophagy in yeast. Biochim. Biophys. Acta 2009, 1793:1404-1412.
33. Lafora G.R., Glueck B. Beitrag zur Histopathologie der myoklonischen Epilepsie. Zeitschrift für die gesamte Neurologie und Psychiatrie 1911, 6:1-14.
34. Lee J.A., Beigneux A., Ahmad S.T., Young S.G., Gao F.B. ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration. Curr. Biol. 2007, 17:1561-1567.
35. Lee J.H., Yu W.H., Kumar A., Lee S., Mohan P.S., Peterhoff C.M., Wolfe D.M., Martinez-Vicente M., Massey A.C., Sovak G., Uchiyama Y., Westaway D., Cuervo A.M., Nixon R.A. Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell 2010, 141:1146-1158.
36. Levine B., Klionsky D.J. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 2004, 6:463-477.
37. Levine B., Kroemer G. Autophagy in aging, disease and death: the true identity of a cell death impostor. Cell Death Differ. 2009, 16:1-2.
38. Martinez-Vicente M., Talloczy Z., Wong E., Tang G., Koga H., Kaushik S., de Vries R., Arias E., Harris S., Sulzer D., Cuervo A.M. Cargo recognition failure is responsible for inefficient autophagy in Huntington's disease. Nat. Neurosci. 2010, 13:567-576.
39. Meijer A.J., Codogno P. Signalling and autophagy regulation in health, aging and disease. Mol. Aspects Med. 2006, 27:411-425.
40. Menzies F.M., Ravikumar B., Rubinsztein D.C. Protective roles for induction of autophagy in multiple proteinopathies. Autophagy 2006, 2:224-225.
41. Menzies F.M., Huebener J., Renna M., Bonin M., Riess O., Rubinsztein D.C. Autophagy induction reduces mutant ataxin-3 levels and toxicity in a mouse model of spinocerebellar ataxia type 3. Brain 2010, 133:93-104.
42. Minassian B.A., Lee J.R., Herbrick J.A., Huizenga J., Soder S., Mungall A.J., Dunham I., Gardner R., Fong C.Y., Carpenter S., Jardim L., Satishchandra P., Andermann E., Snead O.C., Lopes-Cendes I., Tsui L.C., Delgado-Escueta A.V., Rouleau G.A., Scherer S.W. Mutations in a gene encoding a novel protein tyrosine phosphatase cause progressive myoclonus epilepsy. Nat. Genet. 1998, 20:171-174.
43. Mizushima N. Autophagy: process and function. Genes Dev. 2007, 21:2861-2873.
44. Nakatogawa H., Ichimura Y., Ohsumi Y. Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion. Cell 2007, 130:165-178.
45. Noda T., Ohsumi Y. Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J. Biol. Chem. 1998, 273:3963-3966.
46. Orsi A., Polson H.E., Tooze S.A. Membrane trafficking events that partake in autophagy. Curr. Opin. Cell Biol. 2010, 22:150-156.
47. Pandey U.B., Nie Z., Batlevi Y., McCray B.A., Ritson G.P., Nedelsky N.B., Schwartz S.L., DiProspero N.A., Knight M.A., Schuldiner O., Padmanabhan R., Hild M., Berry D.L., Garza D., Hubbert C.C., Yao T.P., Baehrecke E.H., Taylor J.P. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 2007, 447:859-863.
48. Pankiv S., Clausen T.H., Lamark T., Brech A., Bruun J.A., Outzen H., Overvatn A., Bjorkoy G., Johansen T. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J. Biol. Chem. 2007, 282:24131-24145.
49. Parkinson N., Ince P.G., Smith M.O., Highley R., Skibinski G., Andersen P.M., Morrison K.E., Pall H.S., Hardiman O., Collinge J., Shaw P.J., Fisher E.M. ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B). Neurology 2006, 67:1074-1077. MRC Proteomics in ALS Study; FReJA Consortium.
50. Pickford F., Masliah E., Britschgi M., Lucin K., Narasimhan R., Jaeger P.A., Small S., Spencer B., Rockenstein E., Levine B., Wyss-Coray T. The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice. J. Clin. Invest. 2008, 118:2190-2199.
51. Ramachandran N., Munteanu I., Wang P., Aubourg P., Rilstone J.J., Israelian N., Naranian T., Paroutis P., Guo R., Ren Z.P., Nishino I., Chabrol B., Pellissier J.F., Minetti C., Udd B., Fardeau M., Tailor C.S., Mahuran D.J., Kissel J.T., Kalimo H., Levy N., Manolson M.F., Ackerley C.A., Minassian B.A. VMA21 deficiency causes an autophagic myopathy by compromising V-ATPase activity and lysosomal acidification. Cell 2009, 137:235-246.
52. Ravikumar B., Vacher C., Berger Z., Davies J.E., Luo S., Oroz L.G., Scaravilli F., Easton D.F., Duden R., O'Kane C.J., Rubinsztein D.C. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat. Genet. 2004, 36:585-595.
53. Ravikumar B., Acevedo-Arozena A., Imarisio S., Berger Z., Vacher C., O'Kane C.J., Brown S.D., Rubinsztein D.C. Dynein mutations impair autophagic clearance of aggregate-prone proteins. Nat. Genet. 2005, 37:771-776.
54. Ravikumar B., Berger Z., Vacher C., O'Kane C.J., Rubinsztein D.C. Rapamycin pre-treatment protects against apoptosis. Hum. Mol. Genet. 2006, 15:1209-1216.
55. Ravikumar B., Imarisio S., Sarkar S., O'Kane C.J., Rubinsztein D.C. Rab5 modulates aggregation and toxicity of mutant huntingtin through macroautophagy in cell and fly models of Huntington disease. J. Cell Sci. 2008, 121:1649-1660.
56. Ravikumar B., Futter M., Jahreiss L., Korolchuk V.I., Lichtenberg M., Luo S., Massey D.C., Menzies F.M., Narayanan U., Renna M., Jimenez-Sanchez M., Sarkar S., Underwood B., Winslow A., Rubinsztein D.C. Mammalian macroautophagy at a glance. J. Cell Sci. 2009, 122:1707-1711.
57. Ravikumar B., Moreau K., Jahreiss L., Puri C., Rubinsztein D.C. Plasma membrane contributes to the formation of pre-autophagosomal structures. Nat. Cell Biol. 2010, 12:747-757.
58. Rose C., Menzies F.M., Renna M., Acevedo-Arozena A., Corrochano S., Sadiq O., Brown S.D., Rubinsztein D.C. Rilmenidine attenuates toxicity of polyglutamine expansions in a mouse model of Huntington's disease. Hum. Mol. Genet. 2010, 19:2144-2153.
59. Ross O.A., Braithwaite A.T., Skipper L.M., Kachergus J., Hulihan M.M., Middleton F.A., Nishioka K., Fuchs J., Gasser T., Maraganore D.M., Adler C.H., Larvor L., Chartier-Harlin M.C., Nilsson C., Langston J.W., Gwinn K., Hattori N., Farrer M.J. Genomic investigation of alpha-synuclein multiplication and parkinsonism. Ann. Neurol. 2008, 63:743-750.
60. Rubinsztein D.C. The roles of intracellular protein-degradation pathways in neurodegeneration. Nature 2006, 443:780-786.
61. Rusten T.E., Vaccari T., Lindmo K., Rodahl L.M., Nezis I.P., Sem-Jacobsen C., Wendler F., Vincent J.P., Brech A., Bilder D., Stenmark H. ESCRTs and Fab1 regulate distinct steps of autophagy. Curr. Biol. 2007, 17:1817-1825.
62. Rusten T.E., Filimonenko M., Rodahl L.M., Stenmark H., Simonsen A. ESCRTing autophagic clearance of aggregating proteins. Autophagy 2008, 4:233-236.
63. Sancak Y., Peterson T.R., Shaul Y.D., Lindquist R.A., Thoreen C.C., Bar-Peled L., Sabatini D.M. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 2008, 320:1496-1501.
64. Sancak Y., Bar-Peled L., Zoncu R., Markhard A.L., Nada S., Sabatini D.M. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 2010, 141:290-303.
65. Sarbassov D.D., Ali S.M., Sabatini D.M. Growing roles for the mTOR pathway. Curr. Opin. Cell Biol. 2005, 17:596-603.
66. Sarkar S., Rubinsztein D.C. Small molecule enhancers of autophagy for neurodegenerative diseases. Mol. Biosyst. 2008, 4:895-901.
67. Sarkar S., Floto R.A., Berger Z., Imarisio S., Cordenier A., Pasco M., Cook L.J., Rubinsztein D.C. Lithium induces autophagy by inhibiting inositol monophosphatase. J. Cell Biol. 2005, 170:1101-1111.
68. Sarkar S., Perlstein E.O., Imarisio S., Pineau S., Cordenier A., Maglathlin R.L., Webster J.A., Lewis T.A., O'Kane C.J., Schreiber S.L., Rubinsztein D.C. Small molecules enhance autophagy and reduce toxicity in Huntington's disease models. Nat. Chem. Biol. 2007, 3:331-338.
69. Sarkar S., Krishna G., Imarisio S., Saiki S., O'Kane C.J., Rubinsztein D.C. A rational mechanism for combination treatment of Huntington's disease using lithium and rapamycin. Hum. Mol. Genet. 2008, 17:170-178.
70. Sarkar S., Ravikumar B., Floto R.A., Rubinsztein D.C. Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathies. Cell Death Differ. 2009, 16:46-56.
71. Settembre C., Fraldi A., Jahreiss L., Spampanato C., Venturi C., Medina D., de Pablo R., Tacchetti C., Rubinsztein D.C., Ballabio A. A block of autophagy in lysosomal storage disorders. Hum. Mol. Genet. 2008, 17:119-129.
72. Shibata M., Lu T., Furuya T., Degterev A., Mizushima N., Yoshimori T., MacDonald M., Yankner B., Yuan J. Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1. J. Biol. Chem. 2006, 281:14474-14485.
73. Shin H.W., Hayashi M., Christoforidis S., Lacas-Gervais S., Hoepfner S., Wenk M.R., Modregger J., Uttenweiler-Joseph S., Wilm M., Nystuen A., Frankel W.N., Solimena M., De Camilli P., Zerial M. An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway. J. Cell Biol. 2005, 170:607-618.
74. Skibinski G., Parkinson N.J., Brown J.M., Chakrabarti L., Lloyd S.L., Hummerich H., Nielsen J.E., Hodges J.R., Spillantini M.G., Thusgaard T., Brandner S., Brun A., Rossor M.N., Gade A., Johannsen P., Sorensen S.A., Gydesen S., Fisher E.M., Collinge J. Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. Nat. Genet. 2005, 37:806-808.
75. Spencer B., Potkar R., Trejo M., Rockenstein E., Patrick C., Gindi R., Adame A., Wyss-Coray T., Masliah E. Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in alpha-synuclein models of Parkinson's and Lewy body diseases. J. Neurosci. 2009, 29:13578-13588.
76. Takamura A., Higaki K., Kajimaki K., Otsuka S., Ninomiya H., Matsuda J., Ohno K., Suzuki Y., Nanba E. Enhanced autophagy and mitochondrial aberrations in murine G(M1)-gangliosidosis. Biochem. Biophys. Res. Commun. 2008, 367:616-622.
77. Tanaka Y., Guhde G., Suter A., Eskelinen E.L., Hartmann D., Lullmann-Rauch R., Janssen P.M., Blanz J., von Figura K., Saftig P. Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice. Nature 2000, 406:902-906.
78. Underwood B.R., Imarisio S., Fleming A., Rose C., Krishna G., Heard P., Quick M., Korolchuk V.I., Renna M., Sarkar S., Garcia-Arencibia M., O'Kane C.J., Murphy M.P., Rubinsztein D.C. Antioxidants can inhibit basal autophagy and enhance neurodegeneration in models of polyglutamine disease. Hum. Mol. Genet. 2010, 19:3413-3429.
79. Urwin H., Authier A., Nielsen J.E., Metcalf D., Powell C., Froud K., Malcolm D.S., Holm I., Johannsen P., Brown J., Fisher E.M., van der Zee J., Bruyland M., Van Broeckhoven C., Collinge J., Brandner S., Futter C., Isaacs A.M. Disruption of endocytic trafficking in frontotemporal dementia with CHMP2B mutations. Hum. Mol. Genet. 2010, 19:2228-2238.
80. Wang T., Lao U., Edgar B.A. TOR-mediated autophagy regulates cell death in Drosophila neurodegenerative disease. J. Cell Biol. 2009, 186:703-711.
81. Webb J.L., Ravikumar B., Atkins J., Skepper J.N., Rubinsztein D.C. Alpha-Synuclein is degraded by both autophagy and the proteasome. J. Biol. Chem. 2003, 278:25009-25013.
82. Webb J.L., Ravikumar B., Rubinsztein D.C. Microtubule disruption inhibits autophagosome-lysosome fusion: implications for studying the roles of aggresomes in polyglutamine diseases. Int. J. Biochem. Cell Biol. 2004, 36:2541-2550.
83. Wei Y., Pattingre S., Sinha S., Bassik M., Levine B. JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol. Cell 2008, 30:678-688.
84. Williams A., Jahreiss L., Sarkar S., Saiki S., Menzies F.M., Ravikumar B., Rubinsztein D.C. Aggregate-prone proteins are cleared from the cytosol by autophagy: therapeutic implications. Curr. Top. Dev. Biol. 2006, 76:89-101.
85. Williams A., Sarkar S., Cuddon P., Ttofi E.K., Saiki S., Siddiqi F.H., Jahreiss L., Fleming A., Pask D., Goldsmith P., O'Kane C.J., Floto R.A., Rubinsztein D.C. Novel targets for Huntington's disease in an mTOR-independent autophagy pathway. Nat. Chem. Biol. 2008, 4:295-305.
86. Winslow A.R., Chen C.W., Corrochano S., Acevedo-Arozena A., Gordon D.E., Peden A.A., Lichtenberg M., Menzies F.M., Ravikumar B., Imarisio S., Brown S., O'Kane C.J., Rubinsztein D.C. alpha-Synuclein impairs macroautophagy: implications for Parkinson's disease. J. Cell Biol. 2010, 190:1023-1037.
87. Yamamoto A., Tagawa Y., Yoshimori T., Moriyama Y., Masaki R., Tashiro Y. Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells. Cell Struct. Funct. 1998, 23:33-42.
88. Yang Z., Klionsky D.J. Mammalian autophagy: core molecular machinery and signaling regulation. Curr. Opin. Cell Biol. 2010, 22:124-131.
89. Yang Y.P., Liang Z.Q., Gu Z.L., Qin Z.H. Molecular mechanism and regulation of autophagy. Acta Pharmacol. Sin. 2005, 26:1421-1434.
90. Yla-Anttila P., Vihinen H., Jokitalo E., Eskelinen E.L. 3D tomography reveals connections between the phagophore and endoplasmic reticulum. Autophagy 2009, 5:1180-1185.
91. Yokoi S., Nakayama H., Negishi T. Biochemical studies on tissues from a patient with Lafora disease. Clin. Chim. Acta 1975, 62:415-423.
92. Zhang L., Yu J., Pan H., Hu P., Hao Y., Cai W., Zhu H., Yu A.D., Xie X., Ma D., Yuan J. Small molecule regulators of autophagy identified by an image-based high-throughput screen. Proc. Natl Acad. Sci. USA 2007, 104:19023-19028.