The DOI matches its Crossref record; 27 of the 28 references it cites were found in a registry or an index.
Impaired Degradation of Mutant α-Synuclein by Chaperone-Mediated Autophagy
Abstract
Aberrant α-synuclein degradation is implicated in Parkinson's disease pathogenesis because the protein accumulates in the Lewy inclusion bodies associated with the disease. Little is known, however, about the pathways by which wild-type α-synuclein is normally degraded. We found that wild-type α-synuclein was selectively translocated into lysosomes for degradation by the chaperone-mediated autophagy pathway. The pathogenic A53T and A30P α-synuclein mutants bound to the receptor for this pathway on the lysosomal membrane, but appeared to act as uptake blockers, inhibiting both their own degradation and that of other substrates. These findings may underlie the toxic gain-of-function by the mutants.
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In the citing paper
“Previous studies suggest that α-synuclein is degraded by macroautophagy, chaperone-mediated autophagy, and the proteasome20–23.”
From Microglia clear neuron-released α-synuclein via selective autophagy and prevent neurodegeneration (2020) · cites this paper as [20]
In the citing paper
“Finally, inhibition of a particular degradative pathway is typically accompanied by an increase in a separate pathway as the cell attempts to compensate for the loss of degradative capacity.158,478,493”
From Guidelines for the use and interpretation of assays for monitoring autophagy (2012) · cites this paper as [493]
In the citing paper
“and animal models with defective lysosomal exocytosis (VAMP7 mice) or defective lysosomal protease activity (Cathepsin D mutant mice) have mild to moderate demyelination.40–42”
From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [42]
In the citing paper
“dopamine-modified α-synuclein blocks chaperone-mediated autophagy [109,110], which induces abnormal intracellular accumulation α-synuclein in PD [120].”
From Degradation of Tyrosine Hydroxylase by the Ubiquitin-Proteasome System in the Pathogenesis of Parkinson’s Disease and Dopa-Responsive Dystonia (2020) · cites this paper as [109]
In the citing paper
“Early evidence suggested roles for CMA and macroautophagy in degrading SNCA/α‐synuclein (Webb et al, 2003; Cuervo et al, 2004).”
From Autophagy in major human diseases (2021) · cites this paper as Cuervo et al, 2004
In the citing paper
“High expression of wild‐type SNCA/α‐synuclein, mutations or unwanted posttranslational modifications on this protein (such as formation of dopamine adducts) is toxic to CMA by preventing multimerization of LAMP2A and subsequent lysosomal internalization of cargo proteins (Cuervo et al, 2004; Martinez‐Vicente et al, 2008).”
From Autophagy in major human diseases (2021) · cites this paper as Cuervo et al, 2004
In the citing paper
“The protein catabolic pathways that regulate synuclein degradation have been discussed by multiple authors4,16,17, and the extent to which autophagy contributes to synuclein degradation depends on the presence of mutations18.”
From Loss of autophagy in dopaminergic neurons causes Lewy pathology and motor dysfunction in aged mice (2018) · cites this paper as [18]
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Pathogenesis of nigral cell death in Parkinson's disease
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“SYN mutants actually bind to Lamp2a with higher affinity blocking their own degradation as well as other CMA substrates (Cuervo et al., 2004).”
BackgroundGlucocerebrosidase is present in α-synuclein inclusions in Lewy body disorders
Göker-Alpan, Ö., Stubblefield, B. K., Giasson, B. I., & Sidransky, E. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0741-7 · Cited by 186
“Furthermore, α-synuclein can be selectively translocated into the lysosomes for degradation by chaperone-mediated autophagy and aggregated forms of α-synuclein may be degraded by lysosomes [6].”
BackgroundSTUB1/CHIP is required for HIF1A degradation by chaperone-mediated autophagy
Ferreira, J. V., Fofo, H., Bejarano, E., Bento, C. F., Ramalho, J. S., Girão, H., & Pereira, P. (2013) · Autophagy · doi:10.4161/auto.25190 · Cited by 187
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“…add complexity to the net role mitophagy failure plays in PD. Mutations of a-synuclein in familial PD also disrupt sub- strate access during CMA by binding abnormally tightly to LAMP2A, thereby blocking not only its own uptake into lysosomes but that of other CMA substrates (Cuervo et al. 2004).”
BackgroundMitochondrial dynamics in Parkinson's disease: a role for α-synuclein?
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“…effects of α-Syn in the presence of caspase activation (Alves Da Costa et al., 2002); and (iv) a role in protein clearance, since mutant α-Syn inhibits lysosomal degradation by binding to lysosome-associated membrane glycoprotein 2A (LAMP2A) and blocking protein uptake (Cuervo et al., 2004).”
BackgroundThe emerging role of α-synuclein truncation in aggregation and disease
Sorrentino, Z. A., & Giasson, B. I. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.011743 · Cited by 184
“The most common proteases in truncating both monomeric and fibrillar asyn are lysosomal proteases, where most physiologic and pathologic asyn is normally degraded (39, 169, 204).”
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Neurodegeneration and Motor Dysfunction in a Conditional Model of Parkinson's Disease
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“The latter may indicate activation of autophagy, which is suggested to accompany aggregation and neurodegeneration (Wang et al., 2006) and which has also been found in cellular systems overexpressing -syn (Cuervo et al., 2004; Sarkar et al., 2007).”
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Stefanis, L., Emmanouilidou, E., Pantazopoulou, M., Kirik, D., Vekrellis, K., & Tofaris, G. K. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14704 · Cited by 183
Self-citationChaperone-assisted degradation: multiple paths to destruction
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All-you-can-eat: autophagy in neurodegeneration and neuroprotection
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“The toxicity of α-syn may be induced through several mechanisms: (a) binding and inhibition of lysosomal function (Cuervo et al. 2004; Flavin et al. 2017); (b) inhibition of proteasome activity (Tanaka et al. 2001; Stefanis et al. 2001; Petrucelli et al. 2002; Lindersson et al. 2004; Smith et al.…”
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“accumulation and aggregation of a-synuclein in the cell ( 15 ).”
BackgroundCell systems and the toxic mechanism(s) of α-synuclein
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“It has also been shown that chaperone mediated autophagy, a protein degradation pathway that depends on lysosomal function and is tightly regulated by cells, is affected by dominant α-synuclein mutations (Cuervo et al., 2004).”
BackgroundAutophagy and pattern recognition receptors in innate immunity
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Lysosomal Dysfunction and α‐Synuclein Aggregation in Parkinson's Disease: Diagnostic Links
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Is Parkinson’s disease a lysosomal disorder?
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“Physiological a-synuclein can be degraded through the lysosomal system (Cuervo et al., 2004) and mutations that perturb lysosomal function are expected to affect a-synuclein levels.”
BackgroundRapid turnover and polyubiquitylation of the retroviral restriction factor TRIM5
Diaz‐Griffero, F., Li, X., Javanbakht, H., Song, B., Welikala, S., Stremlau, M. H., & Sodroski, J. (2006) · Virology · doi:10.1016/j.virol.2005.12.040 · Cited by 174
“Cytoplasmic inclusion bodies associated with neurodegenerative protein aggregates have been shown to be susceptible to autophagic degradation (Ravikumar et al., 2002; Webb et al., 2003; Cuervo et al., 2004; Iwata et al., 2005).”
BackgroundBrain Disorders Due to Lysosomal Dysfunction
Fraldi, A., Klein, A. D., Medina, D. L., & Settembre, C. (2016) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-070815-014031 · Cited by 173
LAMP2A, LAMP2B and LAMP2C: similar structures, divergent roles
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“For example, while wild-type SNCA was selectively translocated into lysosomes for degradation by CMA, its pathogenic variants were less obedi-ent to this autophagic degradation [44].”
BackgroundAlpha-synuclein research: defining strategic moves in the battle against Parkinson’s disease
Oliveira, L. M. A., Gasser, T., Edwards, R. H., Zweckstetter, M., Melki, R., Stefanis, L., Lashuel, H. A., Sulzer, D., Vekrellis, K., Halliday, G. M., et al. (2021) · npj Parkinson s Disease · doi:10.1038/s41531-021-00203-9 · Cited by 174
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“Multiple proteolytic pathways have been reported to be involved in the degradation of a-synuclein, including the proteasome (Bennett et al., 1999; Rott et al., 2011), the endosomal-lysosomal system and autophagy (Cuervo et al., 2004; Tofaris et al., 2011).”
BackgroundLysosomal Dysfunction in Down Syndrome Is APP-Dependent and Mediated by APP-βCTF (C99)
Jiang, Y., Sato, Y., Im, E., Berg, M., Bordi, M., Darji, S., Kumar, A., Mohan, P. S., Bandyopadhyay, U., Diaz, A., et al. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.0578-19.2019 · Cited by 166
“The rates of total protein degradation at the indicated times were calculated as a percentage of total radiolabeled protein degraded to soluble amino acids as described previously (Auteri et al., 1983; Cuervo et al., 2004).”
MethodSelf-citationExosomal secretion of α-synuclein as protective mechanism after upstream blockage of macroautophagy
Fussi, N., Höllerhage, M., Chakroun, T., Nykänen, N.-P., Rösler, T. W., Koeglsperger, T., Wurst, W., Behrends, C., & Höglinger, G. U. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-0816-2 · Cited by 161
α-Synuclein Overexpression Increases Cytosolic Catecholamine Concentration
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“, 2005) or an inhibition of protein degradation via chaperone-mediated autophagy (Cuervo et al., 2004) or the proteosome pathway (Stefanis et al.”
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Autophagy, polyphenols and healthy ageing
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Mendelian forms of Parkinson's disease
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The Complicated Relationship between Gaucher Disease and Parkinsonism: Insights from a Rare Disease
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“It has been suggested that wild-type a-syn is a substrate for CMA, providing a possible link between CMA and PD (Cuervo et al., 2004).”
HMGB1 is involved in autophagy inhibition caused by SNCA/α-synuclein overexpression
Song, J., Lu, J., Liu, L., Chen, L., Durairajan, S. S. K., Yue, Z., Zhang, H., & Li, M. (2013) · Autophagy · doi:10.4161/auto.26751 · Cited by 161
Constitutive autophagy: vital role in clearance of unfavorable proteins in neurons
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Autophagy-mediated clearance of aggresomes is not a universal phenomenon
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Self-citationTargeting AMPK Signaling as a Neuroprotective Strategy in Parkinson’s Disease
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“…and Parkinson’s disease may share a common genetic mechanism, an idea corroborated by the observations that the lysosome is implicated in the clearance of a-synuclein aggregates (Cuervo et al. 2004) and that excessive a-synuclein disrupts neuronal lysosomal function (Mazzulli et al. 2011).”
Backgroundα-Synuclein Suppression by Targeted Small Interfering RNA in the Primate Substantia Nigra
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“Some of these have yet to be tested in cells (Volles et al., 2001; Cuervo et al., 2004), and others were only found with PD-linked mutants (Stefanis et al., 2001; Tanaka et al., 2001; Cuervo et al., 2004).”
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Mitophagy: the latest problem for Parkinson's disease
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“The same a-syn is known to be degraded via the autophagy pathway and, when mutated, can lead to impairment of the autophagy machinery (Cuervo et al. 2004; Pan et al. 2008).”
BackgroundThe lysosome and neurodegenerative diseases
Zhang, L., Sheng, R., & Qin, Z. (2009) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmp031 · Cited by 152
“The pathogenic A53T and A30P a-syn mutants bound to the receptor for this pathway on the lysosomal membrane, but appeared to act as uptake blockers, inhibiting both their own degradation and that of other substrates [ 67 ].”
BackgroundZambon, F., Cherubini, M., Fernandes, H. J. R., Lang, C., Ryan, B. J., Volpato, V., Bengoa‐Vergniory, N., Vingill, S., Attar, M., Booth, H., et al. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz038 · Cited by 165
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“As has been shown by Cuervo et al (2004), the A53T variant blocks chaperone-mediated autophagy,28 and it has been suggested that this may result in an increase in alternate degradative pathways such as macroautophagy.”
BackgroundAutophagy regulates endoplasmic reticulum stress in ischemic preconditioning
Sheng, R., Liu, X.-Q., Zhang, L.-S., Gao, B., Han, R., Wu, Y.-Q., Zhang, X., & Qin, Z. (2012) · Autophagy · doi:10.4161/auto.18673 · Cited by 155
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Cellular proteostasis: degradation of misfolded proteins by lysosomes
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“However, cytosolic aggregates of α-synuclein are also translocated through the lysosomal membrane through chaperone-mediated autophagy, and evidence indicates that pathogenic α-synuclein mutants bind to receptors on the cytosolic face of lysosomal membrane but are poorly translocated to the interior for degradation (C…”
BackgroundKuo, S.-H., Tasset, I., Cheng, M. M., Diaz, A., Pan, M.-K., Lieberman, O. J., Hutten, S. J., Alcalay, R. N., Kim, S., Ximénez-Embún, P., et al. (2022) · Science Advances · doi:10.1126/sciadv.abm6393 · Cited by 153
Self-citationMazzulli, J. R., Mishizen-Eberz, A. J., Giasson, B. I., Lynch, D. R., THOMAS, S. A., Nakashima, A., Nagatsu, T., Ota, A., & Ischiropoulos, H. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0896-06.2006 · Cited by 152
“Previous reports have indicated that expression of -syn induces cellular degeneration that can be attributed to a multitude of events, such as lysosomal and proteosomal dysfunction (Stefanis et al., 2001; Cuervo et al., 2005), sequestration of anti-apoptotic proteins during conditions of oxidative stress (Xu et al.”
BackgroundIssa, A.-R., Sun, J., Petitgas, C., Mesquita, A., Dulac, A., Robin, M., Mollereau, B., Jenny, A., Chérif‐Zahar, B., & Birman, S. (2018) · Autophagy · doi:10.1080/15548627.2018.1491489 · Cited by 156
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Blood–brain barrier alterations and their impact on Parkinson’s disease pathogenesis and therapy
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“, 2004) indicates that excess -synuclein protein can cause DA neuron loss (Cuervo et al., 2004).”
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α-synuclein phosphorylation and truncation are normal events in the adult human brain
Muntané, G., Ferrer, I., & Martínez‐Vicente, M. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.10.042 · Cited by 152
Caffeine and Parkinson’s Disease: Multiple Benefits and Emerging Mechanisms
Ren, X., & Chen, J. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.602697 · Cited by 167
Wong, A. S. L., Lee, R. H. K., Cheung, A. Y., Yeung, P. K. K., Chung, S. K., Cheung, Z. H., & Ip, N. Y. (2011) · Nature Cell Biology · doi:10.1038/ncb2217 · Cited by 155
New Insights into Toxicity and Drug Testing
Gowder, S. J. (2013) · InTech eBooks · doi:10.5772/55886 · Cited by 149
C. elegans as a model organism to investigate molecular pathways involved with Parkinson's disease
Harrington, A. J., Hamamichi, S., Caldwell, G. A., & Caldwell, K. A. (2010) · Developmental Dynamics · doi:10.1002/dvdy.22231 · Cited by 151
“, 2008; Nonaka and Hasegawa, 2009) and lysosomes by means of macroautophagy or chaperone-mediated autophagy (Webb et al., 2003; Cuervo et al., 2004), and conversely, treatment with proteasome or lysosome inhibitors enhance its aggregation (Sawada et al.”
BackgroundDysfunction of Cellular Proteostasis in Parkinson’s Disease
Lehtonen, Š., Sonninen, T.-M., Wojciechowski, S., Goldsteins, G., & Koıstınaho, J. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00457 · Cited by 152
“The link between α-SYN and CMA was initially established in purified lysosomes demonstrating that α-SYN could be actively degraded by CMA (Cuervo et al., 2004).”
BackgroundTenreiro, S., Reimão-Pinto, M. M., Antas, P., Rino, J., Wawrzycka, D., Macedo, D., Rosado-Ramos, R., Amen, T., Waiss, M., Magalhães, F., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004302 · Cited by 154
Lee, J. K., Jin, H. K., Park, M. H., Kim, B.-R., Lee, P. H., Nakauchi, H., Carter, J., He, X., Schuchman, E. H., & Bae, J. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20132451 · Cited by 149
“Metabolic analysis of protein turnover (Cuervo et al., 2004) was assessed using fibroblasts from WT, APP/PS1, and APP/PS1/ASM+/ mice.”
MethodDisruption of Protein Quality Control in Parkinson's DiseasePreprint
Cook, C. N., Stetler, C. T., & Petrucelli, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009423 · Cited by 153
“a-synuclein mutants remain tightly bound to the lysosomal membrane, also interfering with the degradation of other CMA substrates (Cuervo et al. 2004).”
BackgroundInfluentialRocha, E. M., Smith, G. A., Park, E. Y. H., Cao, H., Graham, A.-R., Brown, E., McLean, J. R., Hayes, M. A., Beagan, J. A., Izen, S. C., et al. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6307 · Cited by 149
Effect of autophagy on multiple myeloma cell viability
Hoang, B. Q., Benavides, A., Shi, Y., Frost, P., & Lichtenstein, A. K. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-1177 · Cited by 151
The Role of Glucocerebrosidase Mutations in Parkinson Disease and Lewy Body Disorders
Velayati, A., Yu, W. H., & Sidransky, E. (2010) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-010-0102-x · Cited by 151
Neuronal autophagy and mitophagy in Parkinson's disease
Lizama, B. N., & Chu, C. T. (2021) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2021.100972 · Cited by 152
Genetic and Chemical Activation of TFEB Mediates Clearance of Aggregated α-Synuclein
Kilpatrick, K., Zeng, Y., Hancock, T., & Segatori, L. (2015) · PLoS ONE · doi:10.1371/journal.pone.0120819 · Cited by 145
Ahmed, I., Liang, Y., Schools, S., Dawson, V. L., Dawson, T. M., & Savitt, J. M. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0209-12.2012 · Cited by 144
“Interestingly, aberrant A53T -synuclein is thought to be associated specifically with CMA (Cuervo et al., 2004; Winslow et al., 2010).”
BackgroundExploring the link between glucocerebrosidase mutations and parkinsonism
Westbroek, W., Gustafson, A. M., & Sidransky, E. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2011.05.003 · Cited by 145
What causes cell death in Parkinson's disease?
Gupta, A., Dawson, V. L., & Dawson, T. M. (2009) · Annals of Neurology · doi:10.1002/ana.21573 · Cited by 148
McKinnon, C., de Snoo, M. L., Gondard, E., Neudorfer, C., Chau, H., Ngana, S. G., O’Hara, D. M., Brotchie, J. M., Koprich, J. B., Lozano, A. M., et al. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-0894-0 · Cited by 144
Schultheis, P. J., Fleming, S. M., Clippinger, A. K., Lewis, J. M., Tsunemi, T., Giasson, B. I., Dickson, D. W., Mazzulli, J. R., Bardgett, M. E., Haik, K. L., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt057 · Cited by 147
“The lysosomal degradation pathway is particularly important for clearance of aggregated a-synuclein (52), and studies in yeast (14) and in mammalian cell culture, including mouse primary cortical neurons and rat primary mesencephalic dopaminergic neurons, show that the loss of Atp13a2 function results in a-synuclein a…”
BackgroundDisruption of cellular proteostasis by H1N1 influenza A virus causes α-synuclein aggregation
Marreiros, R., Müller‐Schiffmann, A., Trossbach, S. V., Prikulis, I., Hänsch, S., Weidtkamp‐Peters, S., Moreira, A. R., Sahu, S., Soloviev, I., Selvarajah, S., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1906466117 · Cited by 144
Klegeris, A., Giasson, B. I., Zhang, H., Maguire, J. A., Pelech, S., & McGeer, P. L. (2006) · The FASEB Journal · doi:10.1096/fj.06-6183com · Cited by 145
The Mitochondrial Chaperone Protein TRAP1 Mitigates α-Synuclein Toxicity
Butler, E. K., Voigt, A., Lutz, A. K., Toegel, J. P., Gerhardt, E., Karsten, P., Falkenburger, B. H., Reinartz, A., Winklhofer, K. F., & Schulz, J. B. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002488 · Cited by 144
Malkus, K. A., Tsika, E., & Ischiropoulos, H. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-24 · Cited by 144
“and other CMA substrates [55,187].”
BackgroundAwareness and current knowledge of Parkinson’s disease: a neurodegenerative disorder
Khan, A. U., Akram, M., Daniyal, M., & Zainab, R. (2018) · International Journal of Neuroscience · doi:10.1080/00207454.2018.1486837 · Cited by 151
Pathophysiology of neuropathic lysosomal storage disorders
Bellettato, C. M., & Scarpa, M. (2010) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-010-9075-9 · Cited by 141
“More results emphasize the concept that the lysosomal degradation pathway represents an alternative mechanism for the degradation of proteins, lipids, and damaged organelles and participates in α-synuclein clearance (Cuervo et al. 2004).”
BackgroundAutophagy impairment in Parkinson’s disease
Karabiyik, C., Lee, M. J., & Rubinsztein, D. C. (2017) · Essays in Biochemistry · doi:10.1042/ebc20170023 · Cited by 141
“Autophagy is subcategorized into three types – microautophagy, chaperone-mediated autophagy (CMA) and macroautophagy.”
BackgroundInfluentialMechanisms of protein toxicity in neurodegenerative diseases
Chung, C. G., Lee, H., & Lee, S. B. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2854-4 · Cited by 142
Skibinski, G., Nakamura, K., Cookson, M., & Finkbeiner, S. M. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.2712-13.2014 · Cited by 143
“Given its role in disrupting protein-degradation pathways (Cuervo et al., 2004; Alegre-Abarrategui et al., 2009; Gomez-Suaga et al., 2011), -synuclein might mediate LRRK2 toxicity by disrupting protein homeostasis and changing LRRK2 levels.”
BackgroundInfluentialVMA21 deficiency prevents vacuolar ATPase assembly and causes autophagic vacuolar myopathy
Ramachandran, N., Munteanu, I., Wang, P., Ruggieri, A., Rilstone, J. J., Israelian, N., Naranian, T., Paroutis, P., Guo, R., Ren, Z.-P., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-012-1073-6 · Cited by 139
“[5].”
The Role of Chaperone-Mediated Autophagy in Huntingtin Degradation
Qi, L., Zhang, X., Wu, J.-C., Lin, F., Wang, J., DiFiglia, M., & Qin, Z.-H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046834 · Cited by 136
“In contrast to macroautophagy, a highly specific subset of cytosolic proteins with a motif recognized by the heat-shock cognate protein of 70 kDa chaperone (Hsc70) is selectively degraded in lysosomes via CMA [17,18].”
BackgroundPhosphorylation of LAMP2A by p38 MAPK couples ER stress to chaperone-mediated autophagy
Li, W., Zhu, J., Dou, J., She, H., Tao, K. X., Xu, H., Yang, Q., & Mao, Z. (2017) · Nature Communications · doi:10.1038/s41467-017-01609-x · Cited by 139
“LRRK2: Autophagy and Lysosomal Activity”
Madureira, M., Connor‐Robson, N., & Wade‐Martins, R. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00498 · Cited by 143
“Furthermore, α -synuclein can be degraded via proteasome, CMA, and autophagy in neurons (Webb et al., 2003; Cuervo et al., 2004; Vogiatzi et al., 2008).”
BackgroundIntercellular Spread of Protein Aggregates in Neurodegenerative Disease
Davis, A. A., Leyns, C. E. G., & Holtzman, D. M. (2018) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100617-062636 · Cited by 131
“Failure of lysosomal degradation and autophagy pathways has been implicated in the pathogenesis of synucleinopathies as well, although the precise mechanism of αSyn internalization in neurons also remains unclear (Cuervo et al. 2004).”
BackgroundProtein degradation, aggregation, and misfolding
Cuervo, A. M., Wong, E. S. P., & Martínez‐Vicente, M. (2010) · Movement Disorders · doi:10.1002/mds.22718 · Cited by 142
Self-citationDJ-1 Inhibits α-Synuclein Aggregation by Regulating Chaperone-Mediated Autophagy
Xu, C., Kang, W., Chen, Y., Jiang, T., Zhang, J., Zhang, L., Ding, J., Liu, J., & Chen, S. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00308 · Cited by 143
“…with our research, all of these observations support the idea that several familial PD gene mutations, such as A53T and A30P α-synuclein mutants (Cuervo et al., 2004), I93M UCH-L1 mutant (Kabuta et al., 2008), G2019S LRRK2 mutant (Orenstein et al., 2013) and VPS35 deficiency or mutation (Tang…”
BackgroundResultInfluentialAlpha-synuclein aggregation involves a bafilomycin A1-sensitive autophagy pathway
Klucken, J., Poehler, A.-M., Ebrahimi‐Fakhari, D., Schneider, J., Nuber, S., Rockenstein, E. M., Schlötzer-Schrehardt, U. M., Hyman, B. T., McLean, P. J., Masliah, E., et al. (2012) · Autophagy · doi:10.4161/auto.19371 · Cited by 141
Metadata
- Authors
- Cuervo, A. M., Stefanis, L., Fredenburg, R., Lansbury, P. T., & Sulzer, D.
- Affiliations
- Department of Anatomy and Structural Biology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
- Brigham and Women's Hospital (US)
- Venue
- Science
- Published
- 2004-08-27
- Volume
- 305
- Issue
- 5688
- Pages
- 1292-1295
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2068288454
- Cited by
- 2,024
- References
- 28
- Citations by year
- 2026: 64 · 2025: 77 · 2024: 102 · 2023: 71 · 2022: 107 · 2021: 114 · 2020: 128 · 2019: 114 · 2018: 117 · 2017: 101 · 2016: 95 · 2015: 92 · 2014: 93 · 2013: 108 · 2012: 119
- FWCI
- 34.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG-021904)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- alpha-synuclein, chaperone-mediated autophagy, Parkinson's disease, lysosomal degradation, A53T mutant, Lewy bodies, gain-of-function toxicity, protein degradation pathways
- MeSH terms
- Animals, Autophagy, Cells, Cultured, Glyceraldehyde-3-Phosphate Dehydrogenases, Half-Life, Intracellular Membranes, Lysosomes, Male, Mutation, Nerve Tissue Proteins, Neurons, Protein Binding, Antigens, CD, PC12 Cells, Rats, Wistar, Molecular Chaperones, Amino Acid Motifs, Protein Transport, Mice, Rats, Synucleins, alpha-Synuclein, Lysosomal Membrane Proteins
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