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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 2010 (25)

Title and authors Publication Year
Synphilin-1 attenuates neuronal degeneration in the A53T alpha-synuclein transgenic mouse model
WW Smith, Z Liu, Y Liang, N Masuda, DA Swing, NA Jenkins, NG Copeland, JC Troncoso, M Pletnikov, TM Dawson, LJ Martin, TH Moran, MK Lee, DR Borchelt, CA Ross
Human Molecular Genetics 2010
Tickled PINK1: mitochondrial homeostasis and autophagy in recessive Parkinsonism
CT Chu
Biochimica et Biophysica Acta 2010
Heat Shock Proteins: Cellular and molecular mechanisms in the CNS
RA Stetler, Y Gan, W Zhang, AK Liou, Y Gao, G Cao, J Chen
Progress in Neurobiology 2010
Alpha-synuclein mediates alterations in membrane conductance: a potential role for alpha-synuclein oligomers in cell vulnerability
LR Feng, HJ Federoff, S Vicini, KA Maguire-Zeiss
The European journal of neuroscience 2010
Lysosomal function in macromolecular homeostasis and bioenergetics in Parkinson's disease
L Schneider, J Zhang
Molecular Neurodegeneration 2010
Alpha-synuclein overexpression increases dopamine toxicity in BE2-M17 cells
M Bisaglia, E Greggio, D Maric, DW Miller, MR Cookson, L Bubacco
BMC neuroscience 2010
Lysosomal degradation of alpha-synuclein in vivo
SK Mak, AL McCormack, AB Manning-Bog, AM Cuervo, DA di Monte
The Journal of biological chemistry 2010
Selective molecular alterations in the autophagy pathway in patients with Lewy body disease and in models of alpha-synucleinopathy
L Crews, B Spencer, P Desplats, C Patrick, A Paulino, E Rockenstein, L Hansen, A Adame, D Galasko, E Masliah
PloS one 2010
The Role of Glucocerebrosidase Mutations in Parkinson Disease and Lewy Body Disorders
A Velayati, WH Yu, E Sidransky
Current Neurology and Neuroscience Reports 2010
T cell-microglial dialogue in Parkinson's disease and amyotrophic lateral sclerosis: are we listening?
SH Appel, DR Beers, JS Henkel
Trends in Immunology 2010
Protein Homeostasis and Aging: the importance of exquisite quality control
H Koga, S Kaushik, AM Cuervo
Ageing Research Reviews 2010
Chaperone-mediated Autophagy in Protein Quality Control
E Arias, AM Cuervo
Current Opinion in Cell Biology 2010
Synaptic Dysfunction in Genetic Models of Parkinson's Disease: A Role for Autophagy?
ED Plowey, CT Chu
Neurobiology of Disease 2010
Chaperone-mediated autophagy dysfunction in the pathogenesis of neurodegeneration
H Koga, AM Cuervo
Neurobiology of Disease 2010
Autophagy in Neurodegenerative disorders: Pathogenic Roles and Therapeutic Implications
R Banerjee, MF Beal, B Thomas
Trends in Neurosciences 2010
Chaperone-mediated autophagy: Molecular mechanisms and physiological relevance
SJ Orenstein, AM Cuervo
Seminars in Cell & Developmental Biology 2010
Pathogenic lysosomal depletion in Parkinson's disease
B Dehay, J Bové, N Rodríguez-Muela, C Perier, A Recasens, P Boya, M Vila
The Journal of neuroscience : the official journal of the Society for Neuroscience 2010
Integration of clearance mechanisms: the proteasome and autophagy
E Wong, AM Cuervo
Cold Spring Harbor perspectives in biology 2010
Autophagic pathways and metabolic stress
S Kaushik, R Singh, AM Cuervo
Diabetes, Obesity and Metabolism 2010
Autophagy gone awry in neurodegenerative diseases
E Wong, AM Cuervo
Nature Neuroscience 2010
Basic mechanisms of neurodegeneration: a critical update
KA Jellinger
Journal of Cellular and Molecular Medicine 2010
α-Synuclein impairs macroautophagy: implications for Parkinson’s disease
AR Winslow, CW Chen, S Corrochano, A Acevedo-Arozena, DE Gordon, AA Peden, M Lichtenberg, FM Menzies, B Ravikumar, S Imarisio, S Brown, CJ OKane, DC Rubinsztein
The Journal of Cell Biology 2010
Neurodegenerative dementia and parkinsonism.
Gabelle A, Portet F, Berr C, Touchon J
The journal of nutrition, health & aging 2010
Neuropathology of sporadic Parkinson disease before the appearance of parkinsonism: preclinical Parkinson disease.
Ferrer I, Martinez A, Blanco R, Dalfó E, Carmona M
Journal of neural transmission (Vienna, Austria : 1996) 2010
Chaperone-mediated autophagy: machinery, regulation and biological consequences.
Li W, Yang Q, Mao Z
Cellular and molecular life sciences : CMLS 2010

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