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Citations to this article

Dopamine-modified α-synuclein blocks chaperone-mediated autophagy
Marta Martinez-Vicente, … , David Sulzer, Ana Maria Cuervo
Marta Martinez-Vicente, … , David Sulzer, Ana Maria Cuervo
Published January 2, 2008
Citation Information: J Clin Invest. 2008;118(2):777-788. https://doi.org/10.1172/JCI32806.
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Research Article Neuroscience Article has an altmetric score of 5

Dopamine-modified α-synuclein blocks chaperone-mediated autophagy

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Abstract

Altered degradation of α-synuclein (α-syn) has been implicated in the pathogenesis of Parkinson disease (PD). We have shown that α-syn can be degraded via chaperone-mediated autophagy (CMA), a selective lysosomal mechanism for degradation of cytosolic proteins. Pathogenic mutants of α-syn block lysosomal translocation, impairing their own degradation along with that of other CMA substrates. While pathogenic α-syn mutations are rare, α-syn undergoes posttranslational modifications, which may underlie its accumulation in cytosolic aggregates in most forms of PD. Using mouse ventral medial neuron cultures, SH-SY5Y cells in culture, and isolated mouse lysosomes, we have found that most of these posttranslational modifications of α-syn impair degradation of this protein by CMA but do not affect degradation of other substrates. Dopamine-modified α-syn, however, is not only poorly degraded by CMA but also blocks degradation of other substrates by this pathway. As blockage of CMA increases cellular vulnerability to stressors, we propose that dopamine-induced autophagic inhibition could explain the selective degeneration of PD dopaminergic neurons.

Authors

Marta Martinez-Vicente, Zsolt Talloczy, Susmita Kaushik, Ashish C. Massey, Joseph Mazzulli, Eugene V. Mosharov, Roberto Hodara, Ross Fredenburg, Du-Chu Wu, Antonia Follenzi, William Dauer, Serge Przedborski, Harry Ischiropoulos, Peter T. Lansbury, David Sulzer, Ana Maria Cuervo

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 Total
Citations: 7 20 19 27 31 24 21 18 15 17 24 19 23 33 20 25 17 9 369
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2008 (9)

Title and authors Publication Year
CD4+ T cells mediate cytotoxicity in neurodegenerative diseases
Stanley H. Appel
Journal of Clinical Investigation 2008
Lysosomal enzyme cathepsin D protects against alpha-synuclein aggregation and toxicity
L Qiao, S Hamamichi, KA Caldwell, GA Caldwell, TA Yacoubian, S Wilson, ZL Xie, LD Speake, R Parks, D Crabtree, Q Liang, S Crimmins, L Schneider, Y Uchiyama, T Iwatsubo, Y Zhou, L Peng, YM Lu, DG Standaert, KC Walls, JJ Shacka, KA Roth, J Zhang
Molecular brain 2008
Autophagy in neuroprotection and neurodegeneration: a question of balance
SJ rd, CT Chu
Future Neurology 2008
Cathepsin D is the main lysosomal enzyme involved in the degradation of alpha-synuclein and generation of its carboxy-terminally truncated species
D Sevlever, P Jiang, SH Yen
Biochemistry 2008
Wild type alpha-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells
T Vogiatzi, M Xilouri, K Vekrellis, L Stefanis
The Journal of biological chemistry 2008
Autophagy-mediated clearance of aggresomes is not a universal phenomenon
ES Wong, JM Tan, WE Soong, K Hussein, N Nukina, VL Dawson, TM Dawson, AM Cuervo, KL Lim
Human Molecular Genetics 2008
Oxidative and nitrative protein modifications in Parkinson's disease
SR Danielson, JK Andersen
Free radical biology & medicine 2008
Neuronal pigmented autophagic vacuoles: lipofuscin, neuromelanin, and ceroid as macroautophagic responses during aging and disease
D Sulzer, E Mosharov, Z Talloczy, FA Zucca, JD Simon, L Zecca
Journal of Neurochemistry 2008
Common key-signals in learning and neurodegeneration: focus on excito-amino acids, beta-amyloid peptides and alpha-synuclein.
Agnati LF, Leo G, Genedani S, Piron L, Rivera A, Guidolin D, Fuxe K
Journal of neural transmission (Vienna, Austria : 1996) 2008

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