{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:29:25Z","timestamp":1792056565943,"version":"4.4.0"},"reference-count":30,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5688","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2004,8,27]]},"abstract":"<jats:p>Aberrant \u03b1-synuclein degradation is implicated in Parkinson's disease pathogenesis because the protein accumulates in the Lewy inclusion bodies associated with the disease. Little is known, however, about the pathways by which wild-type \u03b1-synuclein is normally degraded. We found that wild-type \u03b1-synuclein was selectively translocated into lysosomes for degradation by the chaperone-mediated autophagy pathway. The pathogenic A53T and A30P \u03b1-synuclein mutants bound to the receptor for this pathway on the lysosomal membrane, but appeared to act as uptake blockers, inhibiting both their own degradation and that of other substrates. These findings may underlie the toxic gain-of-function by the mutants.<\/jats:p>","DOI":"10.1126\/science.1101738","type":"journal-article","created":{"date-parts":[[2004,8,26]],"date-time":"2004-08-26T17:14:15Z","timestamp":1093540455000},"page":"1292-1295","source":"Crossref","is-referenced-by-count":1841,"title":["Impaired Degradation of Mutant \u03b1-Synuclein by Chaperone-Mediated Autophagy"],"prefix":"10.1126","volume":"305","author":[{"given":"Ana Maria","family":"Cuervo","sequence":"first","affiliation":[{"name":"Department of Anatomy and Structural Biology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA."},{"name":"Neurobiology Laboratory, Foundation of Biomedical Research of the Academy of Athens, Athens 11527, Greece and Department of Neurology and Pathology, Columbia University, New York, NY 10032, USA."},{"name":"Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology, Harvard MedicalSchool, Cambridge, MA 02139, USA."},{"name":"Departments of Psychiatry and Neurology, Columbia University, Department of Neuroscience, New York State Psychiatric Institute, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonidas","family":"Stefanis","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Structural Biology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA."},{"name":"Neurobiology Laboratory, Foundation of Biomedical Research of the Academy of Athens, Athens 11527, Greece and Department of Neurology and Pathology, Columbia University, New York, NY 10032, USA."},{"name":"Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology, Harvard MedicalSchool, Cambridge, MA 02139, USA."},{"name":"Departments of Psychiatry and Neurology, Columbia University, Department of Neuroscience, New York State Psychiatric Institute, New York, NY 10032, 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Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA."},{"name":"Neurobiology Laboratory, Foundation of Biomedical Research of the Academy of Athens, Athens 11527, Greece and Department of Neurology and Pathology, Columbia University, New York, NY 10032, USA."},{"name":"Center for Neurologic Diseases, Brigham and Women's Hospital, Department of Neurology, Harvard MedicalSchool, Cambridge, MA 02139, USA."},{"name":"Departments of Psychiatry and Neurology, Columbia University, Department of Neuroscience, New York State Psychiatric Institute, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sulzer","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Structural Biology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA."},{"name":"Neurobiology Laboratory, Foundation of Biomedical Research of the Academy of Athens, Athens 11527, 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C. Massey G. Sovak A. M. Cuervo unpublished results."},{"key":"e_1_3_1_30_2","first-page":"897","volume":"17","year":"2002","unstructured":"K. Larsen, D. Sulzer, Histol. Histopathol.17, 897 (2002).","journal-title":"Histol. Histopathol."},{"key":"e_1_3_1_31_2","unstructured":"We are very grateful to B. Giasson and V. Lee for providing us with a human-specific monoclonal antibody to \u03b1-synuclein (Syn 211) and to Q. Wang and A. Massey for technicalassistance. This work was supported by the NIH\/National Institute on Aging grant AG021904 (A.M.C.) two National Institute of Neurological Disorders and Stroke Udall Center grants (D.S. and P.L.) the Parkinson's Disease Foundation the Lowenstein Foundation (L.S. and D.S.) the Matheson Foundation (L.S.) a Huntington's Disease Society of America Grant (D.S. and A.M.C.) and the Howard Hughes Medical Institute (A.M.C.). Molecular interaction data have been deposited in the Biomolecular Interaction Network Database with accession code 151734."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1101738","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T22:23:48Z","timestamp":1704839028000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1101738"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,8,27]]},"references-count":30,"journal-issue":{"issue":"5688","published-print":{"date-parts":[[2004,8,27]]}},"alternative-id":["10.1126\/science.1101738"],"URL":"https:\/\/doi.org\/10.1126\/science.1101738","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1020308.239611","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,8,27]]}}}