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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 2009 (17)

Title and authors Publication Year
Tyrosine and Serine Phosphorylation of alpha-Synuclein Have Opposing Effects on Neurotoxicity and Soluble Oligomer Formation
Li Chen, Magali Periquet, Xu Wang, Alessandro Negro, Pamela McLean, Brad Hyman, Mel Feany
Journal of Clinical Investigation 2009
All-you-can-eat: autophagy in neurodegeneration and neuroprotection
PA Jaeger, T Wyss-Coray
Molecular Neurodegeneration 2009
Tau fragmentation, aggregation and clearance: the dual role of lysosomal processing
Y Wang, M Martinez-Vicente, U Krüger, S Kaushik, E Wong, EM Mandelkow, AM Cuervo, E Mandelkow
Human Molecular Genetics 2009
Chaperone-mediated autophagy in health and disease
M Kon, AM Cuervo
FEBS Letters 2009
Stereotaxical infusion of rotenone: a reliable rodent model for Parkinson's disease
N Xiong, J Huang, Z Zhang, Z Zhang, J Xiong, X Liu, M Jia, F Wang, C Chen, X Cao, Z Liang, S Sun, Z Lin, T Wang
PloS one 2009
Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in alpha-synuclein models of Parkinson's and Lewy body diseases
B Spencer, R Potkar, M Trejo, E Rockenstein, C Patrick, R Gindi, A Adame, T Wyss-Coray, E Masliah
The Journal of neuroscience : the official journal of the Society for Neuroscience 2009
Chaperone-mediated autophagy: selectivity pays off
AM Cuervo
Trends in endocrinology and metabolism: TEM 2009
Dopamine-induced conformational changes in alpha-synuclein
TF Outeiro, J Klucken, K Bercury, J Tetzlaff, P Putcha, LM Oliveira, A Quintas, PJ McLean, BT Hyman
PloS one 2009
Mitochondrial kinases in Parkinson's disease: converging insights from neurotoxin and genetic models
RK Dagda, J Zhu, CT Chu
Mitochondrion 2009
Oxidative modifications, mitochondrial dysfunction, and impaired protein degradation in Parkinson's disease: how neurons are lost in the Bermuda triangle
KA Malkus, E Tsika, H Ischiropoulos
Molecular Neurodegeneration 2009
Abberant alpha-synuclein confers toxicity to neurons in part through inhibition of chaperone-mediated autophagy
M Xilouri, T Vogiatzi, K Vekrellis, D Park, L Stefanis
PloS one 2009
Interplay between cytosolic dopamine, calcium, and alpha-synuclein causes selective death of substantia nigra neurons
EV Mosharov, KE Larsen, E Kanter, KA Phillips, K Wilson, Y Schmitz, DE Krantz, K Kobayashi, RH Edwards, D Sulzer
Neuron 2009
Cell death pathways in Parkinson's disease: proximal triggers, distal effectors, and final steps
OA Levy, C Malagelada, LA Greene
Apoptosis : an international journal on programmed cell death 2009
Methods in Enzymology
S Kaushik, AM Cuervo
Methods in enzymology 2009
Basal autophagy induction without AMP-activated protein kinase under low glucose conditions
Williams T, Forsberg LJ, Viollet B, Brenman JE
Autophagy 2009
Molecular and neurochemical mechanisms in PD pathogenesis.
Paris I, Lozano J, Perez-Pastene C, Muñoz P, Segura-Aguilar J
Neurotoxicity Research 2009
The role of dopamine oxidation in mitochondrial dysfunction: implications for Parkinson's disease.
Hastings TG
Journal of Bioenergetics and Biomembranes 2009

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