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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“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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“In addition to the previously cited studies related to the proteasome, another work demonstrated that DAQs modification on αSyn inhibited the chaperone-mediated autophagy (CMA) pathway for other substrates [64], replicating the effects observed with other pathological PDassociated αSyn mutants [65].”
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The autophagy-lysosomal degradation pathway: role in neurodegenerative disease and therapy
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Chapter 19 Methods to Monitor Chaperone‐Mediated Autophagy
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“Proteins can follow different proteolytic pathways depending on changes in the protein itself (posttranslational modifications) or in the cellular conditions that result in activation/inhibition of particular proteolytic pathways (Cuervo, 2004b).”
BackgroundInfluentialSelf-citationPesticide Exposure Exacerbates α-Synucleinopathy in an A53T Transgenic Mouse Model
Norris, E. H., Uryu, K., Leight, S., Giasson, B. I., Trojanowski, J. Q., & Lee, V. M. ‐. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.060359 · Cited by 134
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Schapansky, J., Nardozzi, J. D., & LaVoie, M. J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2014.09.049 · Cited by 132
“Both the ubiquitin-proteosome system (UPS) and the ALP have been implicated (Webb et al., 2003; Cuervo et al., 2004), and again outcomes appear to depend largely on the αSyn conformation being analyzed (for an in depth review see (Xilouri et al., 2013)).”
BackgroundFields, J., Dumaop, W., Elueteri, S., Campos, S., Serger, E., Trejo, M., Kosberg, K., Adame, A., Spencer, B., Rockenstein, E., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.3207-14.2015 · Cited by 133
“Therefore, Tat may interfere with CMA and thereby indirectly increase macroautophagy function as a feedback mechanism to maintain recycling of neuronal components.”
BackgroundInfluentialModels of α-synuclein aggregation in Parkinson’s disease
Giráldez‐Pérez, R. M., Antolín‐Vallespín, M., Muñoz, M.-D., & Sánchez‐Capelo, A. (2014) · Acta Neuropathologica Communications · doi:10.1186/s40478-014-0176-9 · Cited by 140
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The Reaction of α-Synuclein with Tyrosinase
Tessari, I., Bisaglia, M., Valle, F., Samorı̀, B., Bergantino, E., Mammi, S., & Bubacco, L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m709014200 · Cited by 135
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Mitochondrial autophagy in neural function, neurodegenerative disease, neuron cell death, and aging
Batlevi, Y., & Spada, A. R. L. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.09.009 · Cited by 137
Parkinson's disease: convergence on synaptic homeostasis
Soukup, S., Vanhauwaert, R., & Verstreken, P. (2018) · The EMBO Journal · doi:10.15252/embj.201898960 · Cited by 131
“Interestingly, synaptic proteins are significantly enriched for this “KFERQ” recognition motif (Uytterhoeven et al, 2015), and proteins central to PD (a-Synuclein, LRRK2, Tau) also contain this motif (Cuervo et al, 2004; Wang et al, 2009; Orenstein et al, 2013).”
BackgroundChaperone-mediated autophagy: machinery, regulation and biological consequences
Li, W., Yang, Q., & Mao, Z. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0565-6 · Cited by 142
“sequences and have been proved to be CMA substrates [49, 83, 84].”
Backgroundα-Synuclein and Neuronal Cell Death
Yasuda, T., Nakata, Y., & Mochizuki, H. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8327-0 · Cited by 131
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Defective Autophagy in Parkinson’s Disease: Role of Oxidative Stress
Janda, E., Isidoro, C., Carresi, C., & Mollace, V. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8318-1 · Cited by 134
“In fact, upregulation of wild-type (wt) α-synuclein leads to significant inhibition of macroautophagy [68] and mutant forms of α-synuclein A30P and A53T have been shown to inhibit CMA [67, 69].”
BackgroundAl-Wandi, A., Ninkina, N. N., Millership, S. J., Williamson, S. J. M., Jones, P. A., & Buchman, V. L. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.11.001 · Cited by 131
Hanania, R., Sun, H., Xu, K., Pustylnik, S., Jeganathan, S., & Harrison, R. E. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.290676 · Cited by 130
“The autophagy-lysosome pathway is typically responsible for clearing of cytosolic proteins with relatively long half-lives (49).”
BackgroundSu, L., Li, H., Lv, L., Feng, Y., Li, G., Luo, R., Zhou, H., Lei, X., Ma, L., Li, J., et al. (2015) · Autophagy · doi:10.1080/15548627.2015.1082020 · Cited by 128
“In addition, basal levels of autophagy and chaperonemediated autophagy are necessary for the clearance of abnormal SNCA.(27,28) Excessive autophagy has also been associated with neuronal loss.”
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“Autophagic cell death has been demonstrated post-mortem in the midbrains of PD patients (Anglade et al., 1997), and in vitro models, where autophagy is impaired by mutant alphasynuclein protein (Cuervo et al., 2004).”
BackgroundProteasome Regulation of Oxidative Stress in Aging and Age-Related Diseases of the CNS
Ding, Q., Dimayuga, E. R., & Keller, J. N. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.163 · Cited by 129
Interactions between Hsp70 and the Hydrophobic Core of α-Synuclein Inhibit Fibril Assembly
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“For example, over-expression of A30P and A53T mutant of a-synuclein inhibits CMA, in addition to inducing autophagy (Cuervo et al. 2004; Xilouri et al. 2009).”
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Loss of autophagy in dopaminergic neurons causes Lewy pathology and motor dysfunction in aged mice
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Impairment of chaperone-mediated autophagy induces dopaminergic neurodegeneration in rats
Xilouri, M., Brekk, O. R., Polissidis, A., Chrysanthou‐Piterou, M., Kloukina, I., & Stefanis, L. (2016) · Autophagy · doi:10.1080/15548627.2016.1214777 · Cited by 126
Self-citationMitochondrial Dysfunction in Neural Injury
Zhao, X., Lu, M., Yuan, D., Xu, D.-E., Yao, P.-P., Ji, W., Chen, H., Liu, W., Yan, C.-X., Xia, Y., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00030 · Cited by 132
Autophagy: links with the proteasome
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The Etiopathogenesis of Parkinson Disease and Suggestions for Future Research. Part I
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Dual Role of Autophagy in Diseases of the Central Nervous System
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“In familial PD accumulation of mutant α-synuclein (A53T and A30P) in the Lewy bodies is implicated in the disease pathogenesis (Duda et al., 2002; Cuervo et al., 2004).”
BackgroundVariants in saposin D domain of prosaposin gene linked to Parkinson’s disease
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“Terminally damaged proteins that fail to refold are cleared from cells by proteolytic systems to prevent reaggregation and ensuing toxicities (Cuervo et al., 2004; Cohen et al., 2006).”
BackgroundSNCA (α-synuclein)-induced toxicity in yeast cells is dependent on Sir2-mediated mitophagy
Sampaio‐Marques, B., Felgueiras, C., Silva, A., Rodrigues, M. L., Tenreiro, S., Franssens, V., Reichert, A. S., Outeiro, T. F., Winderickx, J., & Ludovico, P. (2012) · Autophagy · doi:10.4161/auto.21275 · Cited by 128
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“-Synuclein mutants implicated in Parkinson’s disease block their own degradation by the chaperone-mediated autophagy pathway, leading to a gain-offunction toxicity (Cuervo et al., 2004).”
BackgroundLiu, H., Wang, P., Song, W., & Sun, X. (2009) · The FASEB Journal · doi:10.1096/fj.09-134296 · Cited by 124
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Neuronal vulnerability in Parkinson disease: Should the focus be on axons and synaptic terminals?
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The protective role of AMP-activated protein kinase in alpha-synuclein neurotoxicity in vitro
Dulović, M., Jovanović, M., Xilouri, M., Stefanis, L., Harhaji-Trajkovic, L. M., Kravic‐Stevovic, T., Paunović, V., Ardah, M. T., El‐Agnaf, O. M. A., Kostić, V., et al. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.11.002 · Cited by 124
“…ubiquitin– proteasome system and lysosomal pathways — macroautophagy (referred to hereafter as autophagy) and chaperone-mediated autophagy, are considered to play an important role in ASYN degradation (Cuervo et al., 2004; Malkus and Ischiropoulos, 2012; Vogiatzi et al., 2008; Webb et al., 2003).”
BackgroundSelf-citationScheiblich, H., Bousset, L., Schwartz, S., Griep, A., Latz, E., Melki, R., & Heneka, M. T. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2100035 · Cited by 122
“Several studies provide evidence for impaired clearance mechanisms in PD, leading to the idea that a-syn can block its own clearance (54, 55).”
BackgroundMitophagy in neurodegeneration and aging
Palikaras, K., & Tavernarakis, N. (2012) · Frontiers in Genetics · doi:10.3389/fgene.2012.00297 · Cited by 126
“, 2007), protein selective chaperone-mediated autophagy (Cuervo et al., 2004), nucleophagy (Mijaljica et al.”
BackgroundKonno, M., Hasegawa, T., Baba, T., Miura, E., Sugeno, N., Kikuchi, A., Fiesel, F. C., Sasaki, T., Aoki, M., Itoyama, Y., et al. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-38 · Cited by 122
“Furthermore, wildtype αSYN has been shown to be degraded by lysosomes through chaperone-mediated autophagy, and decreased lysosomal function has also been observed in PD patients [49-52].”
BackgroundSelective endosomal microautophagy is starvation-inducible inDrosophila
Mukherjee, A., Patel, B., Koga, H., Cuervo, A. M., & Jenny, A. (2016) · Autophagy · doi:10.1080/15548627.2016.1208887 · Cited by 133
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Autophagy and Parkinson’s Disease
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Rac1 Protein Rescues Neurite Retraction Caused by G2019S Leucine-rich Repeat Kinase 2 (LRRK2)
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“chaperone-mediated autophagy (Cuervo et al., 2004; Webb et al., 2003).”
BackgroundInfluentialLysosome‐dependent pathways as a unifying theme in Parkinson's disease
Tofaris, G. K. (2012) · Movement Disorders · doi:10.1002/mds.25136 · Cited by 123
Protein Misfolding and Aggregation in Parkinson's Disease
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Hypoxic stress activates chaperone-mediated autophagy and modulates neuronal cell survival
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“Recently, increasing evidence has indicated that disruption of CMA is correlated with the pathogenesis of Parkinson’s disease (Alvarez-Erviti et al., 2010; Cuervo et al., 2004; Yang et al., 2009) and Alzheimer disease (Liu et al., 2009; Wang et al., 2009).”
Loss of glucocerebrosidase 1 activity causes lysosomal dysfunction and α-synuclein aggregation
Bae, E.-J., Yang, N. Y., Lee, C.-S., Lee, H.-J., Kim, S., Sardi, S. P., & Lee, S. (2015) · Experimental & Molecular Medicine · doi:10.1038/emm.2014.128 · Cited by 119
Etiology and Pathogenesis of Parkinson Disease
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Novel therapeutic strategies for the treatment of protein-misfolding diseases
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SMPD1 mutations, activity, and α‐synuclein accumulation in Parkinson's disease
Alcalay, R. N., Mallett, V., Vanderperre, B., Tavassoly, O., Dauvilliers, Y., Wu, R. Y. J., Ruskey, J. A., Leblond, C. S., Ambalavanan, A., Laurent, S. B., et al. (2019) · Movement Disorders · doi:10.1002/mds.27642 · Cited by 110
The Interplay between Ca2+ Signaling Pathways and Neurodegeneration
Ureshino, R. P., Erustes, A. G., Bassani, T. B., Wachilewski, P., Guarache, G. C., Nascimento, A. C., Costa, A. J., Smaili, S. S., & Pereira, G. J. S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20236004 · Cited by 122
Gao, H., Yang, W., Qi, Z., Lu, L., Duan, C., Zhao, C., & Yang, H. (2012) · Journal of Molecular Biology · doi:10.1016/j.jmb.2012.06.034 · Cited by 117
Neuronal autophagy: a housekeeper or a fighter in neuronal cell survival?
Lee, J.-A. (2012) · Experimental Neurobiology · doi:10.5607/en.2012.21.1.1 · Cited by 119
“It has been demonstrated that inhibition of CMA by mutant protein was accompanied by compensatory activation of macroautophagy [70].”
BackgroundAugmentation of phenotype in a transgenic Parkinson mouse heterozygous for a Gaucher mutation
Fishbein, I., Kuo, Y., Giasson, B. I., & Nussbaum, R. L. (2014) · Brain · doi:10.1093/brain/awu291 · Cited by 119
“In contrast to previous reports (Cuervo et al., 2004; Li et al., 2004), we found no evidence that the SNCAA53T mutation increases the stability of SNCA.”
BackgroundResultNew Perspectives on Roles of Alpha-Synuclein in Parkinson’s Disease
Zhang, G., Xia, Y. F., Wan, F. J., Ma, K., Guo, X., Kou, L., Yin, S., Han, C., Liu, L., Huang, J., et al. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00370 · Cited by 116
“In addition, non-aggregated α-syn, particularly with A30P or A53T mutations, has the ability to impair the lysosomeassociated membrane protein type 2A (LAMP-2A)-mediated uptake of chaperone-mediated autophagy (CMA) substrates into lysosomes (Cuervo et al., 2004).”
BackgroundWu, Y., Li, X., Xie, W., Jankovic, J. J., Le, W., & Pan, T. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.05.008 · Cited by 115
Mollenhauer, B., El‐Agnaf, O. M. A., Marcus, K., Trenkwalder, C., & Schlossmacher, M. G. (2010) · Biomarkers in Medicine · doi:10.2217/bmm.10.90 · Cited by 114
Gao, J., Perera, G., Bhadbhade, M., Halliday, G. M., & Dzamko, N. L. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.008733 · Cited by 119
Gustavsson, E. K., Follett, J., Trinh, J., Barodia, S. K., Real, R., Liu, Z., Grant-Peters, M., Fox, J. D., Appel-Cresswell, S., Stoessl, A. J., et al. (2024) · The Lancet Neurology · doi:10.1016/s1474-4422(24)00121-2 · Cited by 114
“2,3 Monomeric α-synuclein (which is encoded by SNCA ) functions as a vesicular chaperone, 4 but it can aggregate into Lewy body pathology, 5 which is pathognomonic for Parkinson’s disease.”
α-Synuclein Protofibrils Inhibit 26 S Proteasome-mediated Protein Degradation
Zhang, N., Tang, Z., & Liu, C.-W. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m710560200 · Cited by 116
Fighting disease by selective autophagy of aggregate‐prone proteins
Knævelsrud, H., & Simonsen, A. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.04.041 · Cited by 119
The Vicious Cycle Between α ‐Synuclein Aggregation and Autophagic‐Lysosomal Dysfunction
Bellomo, G., Paciotti, S., Gatticchi, L., & Parnetti, L. (2019) · Movement Disorders · doi:10.1002/mds.27895 · Cited by 116
Vellingiri, B., Suriyanarayanan, A., Selvaraj, P., Abraham, K. S., Pasha, M. T., Babu, H. W. S., Gopalakrishnan, A. V., Singaravelu, G., Reddy, J. K., Ayyadurai, N., et al. (2022) · Chemosphere · doi:10.1016/j.chemosphere.2022.134625 · Cited by 114
The role of autophagy in Parkinson's disease: rotenone-based modeling
Xiong, N., Xiong, J., Jia, M., Liu, L., Zhang, X., Chen, Z., Huang, J., Zhang, Z., Hou, L., Luo, Z., et al. (2013) · Behavioral and Brain Functions · doi:10.1186/1744-9081-9-13 · Cited by 117
“Moreover, overexpressions of alpha-synuclein mutants have been reported to activate autophagy [4-6].”
BackgroundSelective Autophagy: Talking with the UPS
Park, C., & Cuervo, A. M. (2013) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-013-9623-7 · Cited by 118
Self-citationRole of Carbonyl Modifications on Aging-Associated Protein Aggregation
Tanase, M., Urbanska, A. M., Zolla, V., Clement, C. C., Huang, L., Morozova, K. S., Follo, C., Goldberg, M., Roda, B., Reschiglian, P., et al. (2016) · Scientific Reports · doi:10.1038/srep19311 · Cited by 118
Molecular mechanisms of α-synuclein and GBA1 in Parkinson’s disease
Stojkovska, I., Krainc, D., & Mazzulli, J. R. (2017) · Cell and Tissue Research · doi:10.1007/s00441-017-2704-y · Cited by 116
“Studies on the cellular clearance of physiological and pathological forms of α-syn indicated an important role for the lysosomal system, suggesting that lysosomal dysfunction could lead to α-syn aggregation (Cuervo et al. 2004; Lee et al. 2004; Vogiatzi et al. 2008).”
Membrane-bound α-synuclein interacts with glucocerebrosidase and inhibits enzyme activity
Yap, T. L., Velayati, A., Sidransky, E., & Lee, J. C. (2012) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2012.11.010 · Cited by 111
A FRET Sensor for Non‐Invasive Imaging of Amyloid Formation in Vivo
Schierle, G. S. K., Bertoncini, C. W., Chan, F. T. S., van der Goot, A. T., Schwedler, S., Skepper, J. N., Schlachter, S. C., van Ham, T. J., Esposito, A., Kumita, J. R., et al. (2011) · ChemPhysChem · doi:10.1002/cphc.201000996 · Cited by 110
Trehalose as a promising therapeutic candidate for the treatment of Parkinson's disease
Khalifeh, M., Barreto, G. E., & Sahebkar, A. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14623 · Cited by 111
“A reduction of CMA activity increases the accumulation of more aggregated proteins and augments degeneration of dopaminergic neurons (Alvarez‐Erviti et al., 2010; Cuervo et al., 2004).”
BackgroundTau in the Pathophysiology of Parkinson’s Disease
Pan, L., Meng, L., He, M., & Zhang, Z. (2021) · Journal of Molecular Neuroscience · doi:10.1007/s12031-020-01776-5 · Cited by 110
“Moreover, the collapse of any pathways involved in α-Syn clearance and degradation results in the accumulation of α-Syn (Cuervo 2004; McNaught et al.”
BackgroundYuan, Y., Yan, W.-F., Sun, J., Huang, J., Mu, Z., & Chen, N. (2014) · Toxicology Letters · doi:10.1016/j.toxlet.2014.11.029 · Cited by 111
“Both the ubiquitin– proteasome system and the autophagy–lysosome pathway have been suggested to contribute to a-synuclein turnover (Cuervo et al., 2004).”
BackgroundPathogenic Mechanisms of Neurodegeneration in Parkinson Disease
Mullin, S., & Schapira, A. H. V. (2015) · Neurologic Clinics · doi:10.1016/j.ncl.2014.09.010 · Cited by 108
The Interplay between Alpha-Synuclein Clearance and Spreading
da Fonseca, T. L., Villar‐Piqué, A., & Outeiro, T. F. (2015) · Biomolecules · doi:10.3390/biom5020435 · Cited by 115
“Monomeric -syn can be actively degraded by both organelles [85,86] that compensate each other upon one’s failure [87].”
BackgroundAutophagy in neurodegenerative diseases: From pathogenic dysfunction to therapeutic modulation
Martínez‐Vicente, M. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.03.005 · Cited by 114
The Proteasome Inhibition Model of Parkinson’s Disease
Bentea, E., Verbruggen, L., & Massie, A. (2016) · Journal of Parkinson s Disease · doi:10.3233/jpd-160921 · Cited by 116
Role of Autophagy in Parkinson’s Disease
Cerri, S., & Blandini, F. (2018) · Current Medicinal Chemistry · doi:10.2174/0929867325666180226094351 · Cited by 107
Synuclein, dopamine and oxidative stress: co-conspirators in Parkinson's disease?
Maguire‐Zeiss, K. A., Short, D. W., & Federoff, H. J. (2004) · Molecular Brain Research · doi:10.1016/j.molbrainres.2004.09.014 · Cited by 115
Glutamate, excitotoxicity, and programmed cell death in parkinson disease
Caudle, W. M., & Zhang, J. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.09.027 · Cited by 107
“Instead of binding with LAMP2a and being internalized for degradation, they block LAMP2a and inhibit the sequestration and subsequent breakdown of other damaged proteins (Cuervo et al., 2004).”
BackgroundTakahashi, M., Ko, L., Kulathingal, J., Jiang, P., Sevlever, D., & Yen, S.-H. C. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05736.x · Cited by 113
“Calpain-1 (Mishizen-Eberz et al., 2003), proteasomes (Liu et al., 2005) or lysosomal proteases (Cuervo et al., 2004) have been implicated in a-Syn degradation.”
BackgroundInfluentialRotenone impairs autophagic flux and lysosomal functions in Parkinson’s disease
Wu, F., Xu, H., Guan, J.-J., Hou, Y., Gu, J., Zhen, X., & Qin, Z. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.11.004 · Cited by 112
“…of a-synuclein can be degraded by macroautophagy (referred to as autophagy), whereas only wild-type a-synuclein, but not Ala30Pro, Ala53Thr and Glu46Lys mutant forms, is degraded by the process of chaperone-mediated autophagy (CMA) (Cuervo et al., 2004; Vogiatzi et al., 2008; Dagda et al., 2013).”
Targeted degradation of ⍺-synuclein aggregates in Parkinson’s disease using the AUTOTAC technology
Lee, J., Sung, K. W., Bae, E.-J., Yoon, D., Kim, D., Lee, J. S., Park, D.-H., Park, D. Y., Mun, S. R., Kwon, S. C., et al. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00630-7 · Cited by 114
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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