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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
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Citations to this article in year 2018 (18)

Title and authors Publication Year
The Role of Free Radicals in Autophagy Regulation: Implications for Ageing
M Pajares, A Cuadrado, N Engedal, Z Jirsova, M Cahova
Oxidative medicine and cellular longevity 2018
Could Alzheimer’s Disease Originate in the Periphery and If So How So?
G Morris, M Berk, M Maes, BK Puri
Molecular Neurobiology 2018
Global quantitative analysis of the human brain proteome in Alzheimer’s and Parkinson’s Disease
L Ping, DM Duong, L Yin, M Gearing, JJ Lah, AI Levey, NT Seyfried
Scientific Data 2018
Association of exercise-induced autophagy upregulation and apoptosis suppression with neuroprotection against pharmacologically induced Parkinson's disease
Y Jang, DJ Hwang, JH Koo, HS Um, NH Lee, DC Yeom, Y Lee, JY Cho
Journal of Exercise Nutrition & Biochemistry 2018
Can Interactions Between α-Synuclein, Dopamine and Calcium Explain Selective Neurodegeneration in Parkinson's Disease?
MR Post, OJ Lieberman, EV Mosharov
Frontiers in neuroscience 2018
Chronic Caffeine Treatment Protects Against α-Synucleinopathy by Reestablishing Autophagy Activity in the Mouse Striatum
Y Luan, X Ren, W Zheng, Z Zeng, Y Guo, Z Hou, W Guo, X Chen, F Li, JF Chen
Frontiers in neuroscience 2018
Salidroside Promotes the Pathological α-Synuclein Clearance Through Ubiquitin-Proteasome System in SH-SY5Y Cells
T Li, Y Feng, R Yang, L Wu, R Li, L Huang, Q Yang, J Chen
Frontiers in pharmacology 2018
Is Parkinson’s disease a lysosomal disorder?
AD Klein, JR Mazzulli
Brain 2018
Emerging disease-modifying strategies targeting α-synuclein for the treatment of Parkinson's disease: Targeting α-synuclein for treatment of Parkinson's disease
DM O'Hara, SK Kalia, LV Kalia
British Journal of Pharmacology 2018
The Convergence of Dopamine and α-Synuclein: Implications for Parkinson’s Disease
DE Mor, H Ischiropoulos
Journal of Experimental Neuroscience 2018
A Focus on the Beneficial Effects of Alpha Synuclein and a Re-Appraisal of Synucleinopathies
L Ryskalin, CL Busceti, F Limanaqi, F Biagioni, S Gambardella, F Fornai
Current protein & peptide science 2018
Dysregulation of the autophagic-lysosomal pathway in Gaucher and Parkinson's disease
C Pitcairn, WY Wani, JR Mazzulli
Neurobiology of Disease 2018
The coming of age of chaperone-mediated autophagy
S Kaushik, AM Cuervo
Nature Reviews Molecular Cell Biology 2018
Targeting Chaperone-Mediated Autophagy for Disease Therapy
Li W, Dou J, Yang J, Xu H, She H
Current Pharmacology Reports 2018
Activating Autophagy as a Therapeutic Strategy for Parkinson's Disease.
Fowler AJ, Moussa CE
CNS Drugs 2018
Neurotoxins as Preclinical Models for Parkinson's Disease.
Segura-Aguilar J
Neurotoxicity Research 2018
Malfunctioning of Chaperone-Mediated Autophagy in Parkinson's Disease: Feats, Constraints, and Flaws of Modulators.
Tripathi MK, Rajput C, Mishra S, Rasheed MSU, Singh MP
Neurotoxicity Research 2018
Crosstalk between presynaptic trafficking and autophagy in Parkinson’s disease
Pan PY, Zhu Y, Shen Y, Yue Z
Neurobiology of Disease 2018

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