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]
Citations
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Williams, E. T., Chen, X., Otero, P. A., & Moore, D. J. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105768 · Cited by 51
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“, and α-syn mutants (A30P and A53T) block chaperone-mediated autophagy”
BackgroundTriptolide Promotes the Clearance of α-Synuclein by Enhancing Autophagy in Neuronal Cells
Hu, G., Gong, X., Wang, L., Liu, M., Liu, Y., Fu, X., Wang, W., Zhang, T., & Wang, X. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-9808-3 · Cited by 50
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Autophagy and LRRK2 in the Aging Brain
Albanese, F., Novello, S., & Morari, M. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01352 · Cited by 53
“Regarding CMA, similar to α-syn (Cuervo et al., 2004), LRRK2 bears different KFERQ peptide motifs in its amino acid sequence that can be targeted by hsc70.”
BackgroundPedrioli, G., & Paganetti, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.595515 · Cited by 50
Duka, T., & Sidhu, A. (2006) · Neurotoxicity Research · doi:10.1007/bf03033329 · Cited by 51
“MPTP/MPP+-induced aggregation of αSyn, in particular, is a known potent blocker of both the proteasomal and lysosomal protein degradation pathways (Meredith et al., 2002; Cuervo et al., 2004).”
BackgroundPukaß, K., Goldbaum, O., & Richter‐Landsberg, C. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13256 · Cited by 49
“For example, soluble (so) a-syn has been described to be degraded by the UPS, autophagy, and also by chaperone-mediated autophagy (Tofaris et al. 2001; Webb et al. 2003; Cuervo et al. 2004; Vogiatzi et al. 2008).”
BackgroundPantazopoulou, M., Brembati, V., Kanellidi, A., Bousset, L., Melki, R., & Stefanis, L. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15174 · Cited by 50
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Role of Autophagy Pathway in Parkinson’s Disease and Related Genetic Neurological Disorders
Themistokleous, C., Bagnoli, E., Parulekar, R., & Muqit, M. M. K. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168144 · Cited by 51
Khawaja, R. R., Martín‐Segura, A., Santiago‐Fernández, O., Sereda, R., Lindenau, K. L., McCabe, M., Macho‐González, A., Jafari, M., Scrivo, A., Gómez‐Sintes, R., et al. (2025) · Nature Aging · doi:10.1038/s43587-024-00799-6 · Cited by 56
“CMA malfunction also occurs in age-related diseases such as Alzheimer’s disease (AD) 22 , Parkinson’s disease 23,24 , diabetes mellitus 25 and atherosclerosis 26 .”
Self-citationIdentification of a lung cancer cell line deficient in atg7-dependent autophagy
Mandelbaum, J., Rollins, N., Shah, P., Bowman, D., Lee, J. Y., Tayber, O., Bernard, H., Leroy, P. J., Li, P., Koenig, E. M., et al. (2015) · Autophagy · doi:10.1080/15548627.2015.1056966 · Cited by 49
Role of autophagy and its significance in cellular homeostasis
Awan, M. U. F., & Deng, Y. (2014) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-014-5721-8 · Cited by 49
“…components along with harmful proteins and malfunctioning organelles are recycled and assembled back to the cell again; autophagy continues this process of recycling to maintain the balance in the cell, especially in nondividing differentiated cells such as the heart and brain (Cuervo et al. 2004).”
Cui, W., Zhan, Y., Shao, X., Fu, W., Xiao, D., Zhu, J., Qin, X., Zhang, T., Zhang, M., Zhou, Y., et al. (2019) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.9b10308 · Cited by 49
Sanyal, A., Novis, H. S., Gasser, E., Lin, S. C., & LaVoie, M. J. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00442 · Cited by 50
“Furthermore, αSyn proteostasis is fundamentally linked to LRRK2 activity (Cuervo et al., 2004; Fornai et al., 2005; Schapansky et al., 2018).”
BackgroundNie, T., Tao, K., Zhu, L., Huang, L. H., Hu, S., Yang, R., Xu, P., Mao, Z., & Yang, Q. (2020) · Autophagy · doi:10.1080/15548627.2020.1848128 · Cited by 51
Yang, J., Zhang, W., Zhang, S., Iyaswamy, A., Sun, J., Wang, J., & Yang, C. (2023) · Aging and Disease · doi:10.14336/ad.2022.0927 · Cited by 49
Riedel, M. J., Goldbaum, O., & Richter‐Landsberg, C. (2009) · Journal of Molecular Neuroscience · doi:10.1007/s12031-009-9190-y · Cited by 48
“Degradation of αsynuclein occurs by both the proteasome and lysosomal pathways (Tofaris et al. 2001; Webb et al. 2003; Lee et al. 2004a, b; Cuervo et al. 2004), and the co-chaperone CHIP (carboxyl terminus of Hsp70-interacting protein) has been suggested to be involved as a molecular switch between…”
BackgroundParkinson's disease: 10 years of progress, 1997–2007
Fahn, S. (2010) · Movement Disorders · doi:10.1002/mds.22796 · Cited by 51
The unlikely partnership between LRRK 2 and α‐synuclein in Parkinson's disease
Cresto, N., Gardier, C., Gubinelli, F., Gaillard, M., Liot, G., West Andrew, B., & Brouillet, E. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14182 · Cited by 49
“While fewer studies have explored LRRK2 function in the UPS and ALP, LRRK2 contains several CMA- targeting motifs suggesting its possible degradation by CMA.”
BackgroundInfluentialMiller, R. M., Kiser, G. L., Kaysser-Kranich, T., Casaceli, C., Colla, E., Lee, M. K., Palaniappan, C., & Federoff, H. J. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2006.12.005 · Cited by 47
α-Synuclein mutations cluster around a putative protein loop
Kara, E., Lewis, P. A., Ling, H., Proukakis, C., Houlden, H., & Hardy, J. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.04.058 · Cited by 46
New strategies for neuroprotection in glaucoma, a disease that affects the central nervous system
Nucci, C., Russo, R., Martucci, A., Giannini, C., Garaci, F. G., Floris, R., Bagetta, G., & Morrone, L. A. (2016) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2016.04.030 · Cited by 47
“…evolutionarily conserved process by which eukaryotic cells regulate the turnover of long-lived proteins and cytoplasmic organelles and it gained recent attention for its involvement in the pathophysiology of several, including neurodegenerative, diseases (Cuervo et al., 2004; Glick et al., 2010).”
Striatal astrocytes engulf dopaminergic debris in Parkinson's disease: A study in an animal model
Moráles, I., Sánchez, A., Rodriguez‐Sabate, C., & Rodrı́guez, M. (2017) · PLoS ONE · doi:10.1371/journal.pone.0185989 · Cited by 50
Seki, T., Yoshino, K.-I., Tanaka, S., Dohi, E., Onji, T., Yamamoto, K., Hide, I., Paulson, H. L., Saito, N., & Sakai, N. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031232 · Cited by 48
“Although there are several reports concerning CMA in Parkinson’s disease [8,9,10,11] and Alzheimer’s disease [12,13], the role of CMA in various neuronal functions and in other neurodegenerative diseases remains unknown.”
BackgroundLim, A. P. C., & Kraut, R. S. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.2582-08.2009 · Cited by 45
“Disease progression is accompanied by a failure of degradative functions (Nixon et al., 2001; Bahr and Bendiske, 2002), and other evidence directly links the activities of some disease-related proteins to degradation ( Cuervo et al., 2004; Small and Gandy, 2006).”
BackgroundGranek, Z., Barczuk, J., Siwecka, N., Rozpędek‐Kamińska, W., Kucharska, E., & Majsterek, I. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032044 · Cited by 50
Bayati, A., & McPherson, P. S. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107742 · Cited by 47
“Recent research indicates that a -syn also plays a role in cellular stress, cellular homeostasis, and mRNA stability (36 – 40). a -syn levels are indicators of cellular health when it comes to autophagy (41 – 44), speci fi cally chaperone-mediated autophagy (CMA) (45 – 47).”
BackgroundInfluentialSong, L.-K., Ma, K., Yuan, Y., Mu, Z., Song, X., Niu, F., Han, N., & Chen, N. (2015) · PLoS ONE · doi:10.1371/journal.pone.0131281 · Cited by 45
“Furthermore, the overexpressed α-syn is able to impact the protein degradation system including the ubiquitin-proteasome system and autophagy [58, 59].”
BackgroundMechanisms of neurodegeneration in idiopathic Parkinson's disease
Schulz, J. B. (2007) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(08)70021-x · Cited by 46
Crosstalk between the proteasome system and autophagy in the clearance of α-synuclein
Yang, F. W., Yang, Y., Mao, C., Liu, L., Zheng, H.-F., Hu, L., & Liu, C.-F. (2013) · Acta Pharmacologica Sinica · doi:10.1038/aps.2013.29 · Cited by 47
A novel and functional variant within the ATG5 gene promoter in sporadic Parkinson's disease
Chen, D., Zhu, C., Wang, X., Feng, X., Pang, S., Huang, W., Hawley, R. G., & Yan, B. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.01.044 · Cited by 48
Impairment of autophagy: From hereditary disorder to drug intoxication
Aki, T., Funakoshi, T., Unuma, K., & Uemura, K. (2013) · Toxicology · doi:10.1016/j.tox.2013.07.001 · Cited by 46
Alpha Synuclein in Parkinson’s Disease
Kragh, C. L., Romero‐Ramos, M., Halliday, G. M., & Jensen, P. H. (2014) · Springer eBooks · doi:10.1007/978-1-4614-5836-4_14 · Cited by 48
Marxreiter, F., Ettle, B., May, V. E. L., Esmer, H., Patrick, C., Kragh, C. L., Klucken, J., Winner, B., Rieß, O., Winkler, J., et al. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.07.004 · Cited by 46
“Previous studies reported that the A30P mutation per se fortifies dysfunction of UPS (Petrucelli et al., 2002), impairs chaperone-mediated autophagy (Cuervo et al., 2004) and its oligomerization process (Conway et al., 1998; Li et al., 2002; Narhi et al., 1999) further accelerating the pathology.”
Svarcbahs, R., Julku, U. H., & Myöhänen, T. T. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.2309-16.2016 · Cited by 49
“…staining distribution in SN is decreased after KYP-2047 administration To determine whether KYP-2047 decreases the amount of aSyn oligomers, as shown previously by Myöhänen et al. (2012), Dokleja et al. (2014), and Savolainen et al. (2014), an oligomerspecific aSyn staining was performed (Fig.”
BackgroundMethodKim, H., Calatayud, C., Guha, S. K., Fernández‐Carasa, I., Berkowitz, L. A., Carballo‐Carbajal, I., Ezquerra, M., Fernández‐Santiago, R., Kapahi, P., Raya, Á., et al. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-0881-7 · Cited by 50
The disorderly conduct of Hsc70 and its interaction with the Alzheimer's-related Tau protein
Taylor, I. R., Ahmad, A., Wu, T., Nordhues, B. A., Bhullar, A., Gestwicki, J. E., & Zuiderweg, E. R. P. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.002234 · Cited by 46
“Hsc70 (HSPA8) and Hsp70 (HSPA1A) levels are elevated in cells containing neurofibrillary tangles, suggesting a relationship with Tau proteostasis (26).”
BackgroundIron Dysregulation in Parkinson’s Disease: Focused on the Autophagy–Lysosome Pathway
Chen, L., Huang, Y., Cui, J., Song, N., & Xie, J. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00390 · Cited by 47
Protein Quality Control Pathways at the Crossroad of Synucleinopathies
de Mattos, E. P., Wentink, A. S., Nussbaum-Krammer, C. I., Hansen, C., Bergink, S., Melki, R., & Kampinga, H. H. (2020) · Journal of Parkinson s Disease · doi:10.3233/jpd-191790 · Cited by 46
Fredriksen, K., Aivazidis, S., Sharma, K., Burbidge, K. J., Pitcairn, C., Zunke, F., Gelyana, E., & Mazzulli, J. R. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2108489118 · Cited by 47
Cellular Responses to Protein Accumulation Involve Autophagy and Lysosomal Enzyme Activation
Butler, D., Brown, Q. B., Chin, D. J., Batey, L., Karim, S. L., Mutneja, M. S., Karanian, D. A., & Bahr, B. A. (2005) · Rejuvenation Research · doi:10.1089/rej.2005.8.227 · Cited by 46
Alpha-Synuclein and Cognitive Decline in Parkinson Disease
Fan, T.-S., Liu, S. C.-H., & Wu, R. (2021) · Life · doi:10.3390/life11111239 · Cited by 47
Neurochemical biomarkers in the differential diagnosis of movement disorders
Mollenhauer, B., & Trenkwalder, C. (2009) · Movement Disorders · doi:10.1002/mds.22510 · Cited by 45
Eps8 is recruited to lysosomes and subjected to chaperone-mediated autophagy in cancer cells
Welsch, T., Younsi, A., Disanza, A., Rodriguez, J. A., Cuervo, A. M., Scita, G., & Schmidt, J. (2010) · Experimental Cell Research · doi:10.1016/j.yexcr.2010.02.020 · Cited by 45
Self-citationPrionoid Proteins in the Pathogenesis of Neurodegenerative Diseases
Wells, C., Brennan, S. E., Keon, M., & Saksena, N. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00271 · Cited by 46
“However, when the body is incapable of effectively clearing these extracellular proteins as a result of aging or other factors, this process facilitates the spread of infectious fibrils to previously healthy neuronal and glial cells (Cuervo et al., 2004).”
BackgroundNascimento, A. C., Erustes, A. G., Reckziegel, P., Bincoletto, C., Ureshino, R. P., Pereira, G. J. S., & Smaili, S. S. (2020) · Neurochemical Research · doi:10.1007/s11064-020-03126-8 · Cited by 46
α-Synuclein, Lrrk2 and Their Interplay In Parkinson‘s Disease
Liu, G., Aliaga, L., & Cai, H. (2012) · Future Neurology · doi:10.2217/fnl.12.2 · Cited by 45
The Etiopathogenesis of Parkinson Disease and Suggestions for Future Research. Part II
Litvan, I., Chesselet, M., Gasser, T., Monte, D. A. D., Parker, D., Hagg, T., Hardy, J., Jenner, P. G., Myers, R. H., Price, D. D., et al. (2007) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318053716a · Cited by 45
“For some it seems obvious: with increasing age, cellular defense mechanisms such as the activity of chaperones may decrease below a certain threshold that is needed to prevent disease initiation (24), a process that may be important in PD (25).”
BackgroundGenetic basis of Parkinson disease
Xiromerisiou, G., Dardiotis, E., Tsimourtou, V., Kountra, P., Paterakis, K. N., Kapsalaki, E. Z., Fountas, K. N., & Hadjigeorgiou, G. M. (2009) · Neurosurgical FOCUS · doi:10.3171/2009.10.focus09220 · Cited by 49
Parkinsons Disease: Genetics and Beyond
Inamdar, N., Arulmozhi, D. K., Tandon, A., & Bodhankar, S. L. (2007) · Current Neuropharmacology · doi:10.2174/157015907780866893 · Cited by 46
“trafficking [91], impaired chaperone-mediatd autophagy [39] and”
α-Synuclein in Parkinson's Disease: Pathogenic Function and Translation into Animal Models
Eschbach, J., & Danzer, K. M. (2013) · Neurodegenerative Diseases · doi:10.1159/000354615 · Cited by 45
Martínez‐Vicente, M., & Vila, M. (2013) · Experimental Neurology · doi:10.1016/j.expneurol.2013.03.005 · Cited by 50
Sala, G., Marinig, D., Riva, C., Arosio, A., Stefanoni, G., Brighina, L., Formenti, M., Alberghina, L., Colangelo, A. M., & Ferrarese, C. (2016) · NeuroToxicology · doi:10.1016/j.neuro.2016.04.018 · Cited by 46
“…role in PD is recognized to be played by intraneuronal accumulation and aggregation of alpha-synuclein, the demonstration that CMA represents the main catabolic system for alpha-synuclein (Cuervo et al., 2004; Mak et al., 2010) has strengthened the link between CMA dysfunction and PD pathology.”
BackgroundChaperone-Based Therapies for Disease Modification in Parkinson’s Disease
Friesen, E. L., de Snoo, M. L., Rajendran, L., Kalia, L. V., & Kalia, S. K. (2017) · Parkinson s Disease · doi:10.1155/2017/5015307 · Cited by 45
Íñigo-Marco, I., Valencia, M., Larrea, L., Bugallo, R., Martínez-Goikoetxea, M., Zuriguel, I., & Arrasate, M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1703420114 · Cited by 44
Ginkgolic acid promotes autophagy-dependent clearance of intracellular alpha-synuclein aggregates
Vijayakumaran, S., Nakamura, Y., Henley, J. M., & Pountney, D. L. (2019) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2019.103416 · Cited by 45
“Previous studies have shown that -syn is preferentially degraded by CMA, yet aggregation-prone PD-linked - 19 syn mutants are not able to be degraded by CMA, binding to the LAMP2A pore and inhibiting lysosomal degradation (Cuervo et al., 2004).”
BackgroundStudying the Pathophysiology of Parkinson’s Disease Using Zebrafish
Barnhill, L. M., Murata, H., & Bronstein, J. M. (2020) · Biomedicines · doi:10.3390/biomedicines8070197 · Cited by 44
Impact of Chaperone-Mediated Autophagy in Brain Aging: Neurodegenerative Diseases and Glioblastoma
Auzmendi-Iriarte, J., & Matheu, A. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.630743 · Cited by 47
Alpha-Synuclein and the Endolysosomal System in Parkinson’s Disease: Guilty by Association
Teixeira, M., Sheta, R., Idi, W., & Oueslati, A. (2021) · Biomolecules · doi:10.3390/biom11091333 · Cited by 46
“This interactive role was also reported with the inhibition of the CMA through the downregulation of LAMP2A, collectively leading to the formation of high molecular weight or detergent-insoluble oligomeric α-syn conformations [48].”
BackgroundDrouin‐Ouellet, J., Legault, E. M., Nilsson, F., Pircs, K., Bouquety, J., Petit, F., Shrigley, S., Birtele, M., Pereira, M., Storm, P., et al. (2022) · Stem Cell Reports · doi:10.1016/j.stemcr.2022.08.010 · Cited by 49
Genetic Mouse Models of Neurodegenerative Diseases
Trancikova, A. K., Ramonet, D., & Moore, D. J. (2011) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-384878-9.00012-1 · Cited by 47
Mitochondrial Metabolism Modulation: A New Therapeutic Approach for Parkinsons Disease
Arduíno, D. M., Esteves, A. R., Oliveira, C. R., & Cardoso, S. M. (2010) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152710790966687 · Cited by 44
The role of SCARB2 as susceptibility factor in Parkinson's disease
Hopfner, F., Schulte, E. C., Mollenhauer, B., Bereznai, B., Knauf, F., Lichtner, P., Zimprich, A., Haubenberger, D., Pirker, W., Brücke, T., et al. (2013) · Movement Disorders · doi:10.1002/mds.25349 · Cited by 46
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New animal models of Parkinson's disease
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Ca2+, autophagy and protein degradation: Thrown off balance in neurodegenerative disease
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Living with the enemy: from protein-misfolding pathologies we know, to those we want to know
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Autophagy in neurons: it is not all about food
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Alpha-synuclein and autophagy as common steps in neurodegeneration
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Parkinson's disease, proteins, and prions: Milestones
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Chaperone-mediated autophagy: roles in neurodegeneration
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Endolysosomal dysfunction in Parkinson's disease: Recent developments and future challenges
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Sulfur-containing Secondary Metabolites as Neuroprotective Agents
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“In addition, a decrease in lysosomal acidification and consequent decline of lysosomal protein turnover has been reported in mice overexpressing α-synuclein (Stefanis et al., 2001; Cuervo et al., 2004).”
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LRRK2 mutant knock-in mouse models: therapeutic relevance in Parkinson's disease
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Morphological and biochemical studies on aging and autophagy
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“A pathogenic role has been suggested for accumulated mutant a-synuclein as it is associated with cellular dysfunction or reduced lysosomal or proteasomal clearance [64–68] in mice, and it is an abundant component of LBs in sporadic PD, and in diffuse LB disease [4].”
Background
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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