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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 2011 (20)

Title and authors Publication Year
Chaperone-Mediated Autophagy Is Required for Tumor Growth
M Kon, R Kiffin, H Koga, J Chapochnick, F Macian, L Varticovski, AM Cuervo
Science Translational Medicine 2011
HMGB1 acts on microglia Mac1 to mediate chronic neuroinflammation that drives progressive neurodegeneration
HM Gao, H Zhou, F Zhang, BC Wilson, W Kam, JS Hong
The Journal of neuroscience : the official journal of the Society for Neuroscience 2011
PARK9-associated ATP13A2 localizes to intracellular acidic vesicles and regulates cation homeostasis and neuronal integrity
D Ramonet, A Podhajska, K Stafa, S Sonnay, A Trancikova, E Tsika, O Pletnikova, JC Troncoso, L Glauser, DJ Moore
Human Molecular Genetics 2011
Progressive neurodegeneration or endogenous compensation in an animal model of Parkinson's disease produced by decreasing doses of alpha-synuclein
JB Koprich, TH Johnston, P Huot, MG Reyes, M Espinosa, JM Brotchie
PloS one 2011
Autophagy and disease: always two sides to a problem
S Sridhar, Y Botbol, F Macian, AM Cuervo
The Journal of Pathology 2011
Autophagy in Dementias: Autophagy in Dementias
CL Kragh, K Ubhi, T Wyss-Corey, E Masliah
Brain Pathology 2011
Control of autophagy as a therapy for neurodegenerative disease
H Harris, DC Rubinsztein
Nature Reviews Neurology 2011
Mitochondrial Dysfunction: The Road to Alpha-Synuclein Oligomerization in PD
AR Esteves, DM Arduíno, DF Silva, CR Oliveira, SM Cardoso
Parkinson's Disease 2011
Diversity in the Regulation of Autophagy and Mitophagy: Lessons from Parkinson's Disease
CT Chu
Parkinson's Disease 2011
Edaravone guards dopamine neurons in a rotenone model for Parkinson's disease
N Xiong, J Xiong, G Khare, C Chen, J Huang, Y Zhao, Z Zhang, X Qiao, Y Feng, H Reesaul, Y Zhang, S Sun, Z Lin, T Wang
PloS one 2011
Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission
L Alvarez-Erviti, Y Seow, AH Schapira, C Gardiner, IL Sargent, MJ Wood, JM Cooper
Neurobiology of Disease 2011
A Lysosomal Lair for a Pathogenic Protein Pair
TM Dawson, VL Dawson
Science Translational Medicine 2011
Chaperone-mediated autophagy at a glance
S Kaushik, U Bandyopadhyay, S Sridhar, R Kiffin, M Martinez-Vicente, M Kon, SJ Orenstein, E Wong, AM Cuervo
Journal of cell science 2011
Gene–environment interactions: key to unraveling the mystery of Parkinson’s disease
HM Gao, JS Hong
Progress in Neurobiology 2011
ATP13A2 regulates mitochondrial bioenergetics through macroautophagy
AM Gusdon, J Zhu, BV Houten, CT Chu
Neurobiology of Disease 2011
Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in nondiabetics)
T Uchiki, KA Weikel, W Jiao, F Shang, A Caceres, D Pawlak, JT Handa, M Brownlee, R Nagaraj, A Taylor
Aging Cell 2011
Mitochondrial dysfunction in genetic animal models of Parkinson's disease
A Trancikova, E Tsika, DJ Moore
Antioxidants & Redox Signaling 2011
A photoconvertible fluorescent reporter to track chaperone-mediated autophagy
H Koga, M Martinez-Vicente, F Macian, VV Verkhusha, AM Cuervo
Nature Communications 2011
Drug Targets from Genetics: Alpha-Synuclein
Danzer KM, McLean PJ
CNS & neurological disorders drug targets 2011
Chaperone-mediated autophagy: Dice's 'wild' idea about lysosomal selectivity.
Cuervo AM
Nature reviews. Molecular cell biology 2011

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