Lewy Body-like α-Synuclein Aggregates Resist Degradation and Impair Macroautophagy
Open accessAbstract
Cytoplasmic α-synuclein (α-syn) aggregates, referred to as Lewy bodies, are pathological hallmarks of a number of neurodegenerative diseases, most notably Parkinson disease. Activation of macroautophagy is suggested to facilitate degradation of certain proteinaceous inclusions, but it is unclear if this pathway is capable of degrading α-syn aggregates. Here, we examined this issue by utilizing cellular models in which intracellular Lewy body-like α-syn inclusions accumulate after internalization of pre-formed α-syn fibrils into α-syn-expressing HEK293 cells or cultured primary neurons. We demonstrate that α-syn inclusions cannot be effectively degraded, even though they co-localize with essential components of both the autophagic and proteasomal protein degradation pathways. The α-syn aggregates persist even after soluble α-syn levels have been substantially reduced, suggesting that once formed, the α-syn inclusions are refractory to clearance. Importantly, we also find that α-syn aggregates impair overall macroautophagy by reducing autophagosome clearance, which may contribute to the increased cell death that is observed in aggregate-bearing cells. Background: α-Synuclein aggregates and macroautophagy are associated with neurodegeneration. Results: Modulation of macroautophagic activity does not affect α-synuclein aggregate levels, although these aggregates cause accumulation of immature autophagosomes. Conclusion: α-Synuclein aggregates are resistant to degradation and impair autophagy by delaying autophagosome maturation. Significance: Understanding the impact of α-synuclein aggregates on autophagy may help elucidate therapies for α-synuclein-mediated neurodegeneration.
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LB-like synuclein aggregates resist degradation and impair autophagy.
“Furthermore, LB-like synuclein aggregates resist degradation and impair autophagy20.”
From Loss of autophagy in dopaminergic neurons causes Lewy pathology and motor dysfunction in aged mice (2018) · cites this paper as [20]
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Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., et al. (1997) · Science · doi:10.1126/science.276.5321.2045 · Cited by 8,240 · see citing works
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605 · see citing works
Pankiv, S., Clausen, T. H., Lamark, T., Brech, A., Bruun, J.-A., Outzen, H., Øvervatn, A., Bjørkøy, G., & Johansen, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702824200 · Cited by 4,578 · see citing works
Methods in Mammalian Autophagy Research
Mizushima, N., Yoshimori, T., & Levine, B. (2010) · Cell · doi:10.1016/j.cell.2010.01.028 · Cited by 4,497 · see citing works
α-Synuclein Locus Triplication Causes Parkinson's Disease
Singleton, A. B., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., Hulihan, M., Peuralinna, T., Dutra, A., Nussbaum, R., et al. (2003) · Science · doi:10.1126/science.1090278 · Cited by 4,383 · see citing works
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006) · Nature · doi:10.1038/nature04724 · Cited by 3,882 · see citing works
AlaSOPro mutation in the gene encoding α-synuclein in Parkinson's disease
Krüger, R., Kuhn, W., Müller, T., Woitalla, D., Graeber, M., Kösel, S., Przuntek, H., Epplen, J. T., Schols, L., & Riess, O. (1998) · Nature Genetics · doi:10.1038/ng0298-106 · Cited by 3,836 · see citing works
Loss of autophagy in the central nervous system causes neurodegeneration in mice
Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J.-I., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., et al. (2006) · Nature · doi:10.1038/nature04723 · Cited by 3,500 · see citing works
The new mutation, E46K, of α‐synuclein causes parkinson and Lewy body dementia
Zarranz, J. J., Alegre, J., Gómez‐Esteban, J. C., Lezcano, E., Ros, R., Ampuero, I., Vidal, L., Hoenicka, J., Rodriguez, O., Atarés, B., et al. (2004) · Annals of Neurology · doi:10.1002/ana.10795 · Cited by 2,737 · see citing works
Luk, K. C., Kehm, V., Carroll, J., Zhang, B., O’Brien, P., Trojanowski, J. Q., & Lee, V. M.-Y. (2012) · Science · doi:10.1126/science.1227157 · Cited by 2,563 · see citing works
Self-citationKimura, S., Noda, T., & Yoshimori, T. (2007) · Autophagy · doi:10.4161/auto.4451 · Cited by 2,278 · see citing works
Autophagosome formation: core machinery and adaptations
Xie, Z., & Klionsky, D. J. (2007) · Nature Cell Biology · doi:10.1038/ncb1007-1102 · Cited by 2,165 · see citing works
Impaired Degradation of Mutant α-Synuclein by Chaperone-Mediated Autophagy
Cuervo, A. M., Stefanis, L., Fredenburg, R., Lansbury, P. T., & Sulzer, D. (2004) · Science · doi:10.1126/science.1101738 · Cited by 2,024 · cited 1× · see citing works
“The demonstration that cells harboring aggregated -syn have partial impairment of autophagy complements prior studies that showed that soluble -syn species may reduce autophagic activity (19, 67, 68).”
Backgroundα-Synuclein is phosphorylated in synucleinopathy lesions
Fujiwara, H., Hasegawa, M., Dohmae, N., Kawashima, A., Masliah, E., Goldberg, M., Shen, J., Takio, K., & Iwatsubo, T. (2002) · Nature Cell Biology · doi:10.1038/ncb748 · Cited by 1,906 · see citing works
Aggresomes, inclusion bodies and protein aggregation
Kopito, R. R. (2000) · Trends in Cell Biology · doi:10.1016/s0962-8924(00)01852-3 · Cited by 1,906 · see citing works
Autophagy Is Activated for Cell Survival after Endoplasmic ReticulumStress
Ogata, M., Hino, S.-I., Saito, A., Morikawa, K., Kondo, S., Kanemoto, S., Murakami, T., Taniguchi, M., Tanii, I., Yoshinaga, K., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01453-06 · Cited by 1,832 · see citing works
Mice Lacking α-Synuclein Display Functional Deficits in the Nigrostriatal Dopamine System
Abeliovich, A., Schmitz, Y., Fariñas, I., Choi-Lundberg, D., Ho, W.-H., Castillo, P. E., Shinsky, N., Verdugo, J. M. G., Armanini, M., Ryan, A., et al. (2000) · Neuron · doi:10.1016/s0896-6273(00)80886-7 · Cited by 1,722 · see citing works
The roles of intracellular protein-degradation pathways in neurodegeneration
Rubinsztein, D. C. (2006) · Nature · doi:10.1038/nature05291 · Cited by 1,625 · see citing works
Volpicelli-Daley, L. A., Luk, K. C., Patel, T. P., Tanik, S. A., Riddle, D. M., Stieber, A., Meaney, D. F., Trojanowski, J. Q., & Lee, V. M.-Y. (2011) · Neuron · doi:10.1016/j.neuron.2011.08.033 · Cited by 1,569 · see citing works
Self-citationKawaguchi, Y., Kovacs, J. J., McLaurin, A. C., Vance, J. M., Ito, A., & Yao, T. (2003) · Cell · doi:10.1016/s0092-8674(03)00939-5 · Cited by 1,529 · see citing works
Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling.
Lee, J., Giordano, S., & Zhang, J. (2012) · Biochemical Journal · doi:10.1042/bj20111451 · Cited by 1,438 · see citing works
α-Synuclein Is Degraded by Both Autophagy and the Proteasome
Webb, J. L., Ravikumar, B., Atkins, J., Skepper, J. N., & Rubinsztein, D. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300227200 · Cited by 1,429 · see citing works
Nix is a selective autophagy receptor for mitochondrial clearance
Novak, I., Kirkin, V., McEwan, D. G., Zhang, J., Wild, P., Rozenknop, A., Rogov, V., Löhr, F., Popovic, D., Occhipinti, A., et al. (2010) · The EMBO Reports · doi:10.1038/embor.2009.256 · Cited by 1,309 · see citing works
Escola, J.-M., Kleijmeer, M. J., Stoorvogel, W., Griffith, J. M., Yoshie, O., & Geuze, H. J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.32.20121 · Cited by 1,228 · see citing works
Boland, B., Kumar, A., Lee, S., Platt, F. M., Wegiel, J., Yu, W. H., & Nixon, R. A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0800-08.2008 · Cited by 1,119 · see citing works
Emmanouilidou, E., Melachroinou, K., Roumeliotis, T., Garbis, S. D., Ntzouni, M., Margaritis, L. H., Stefanis, L., & Vekrellis, K. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5699-09.2010 · Cited by 1,115 · see citing works
Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy
Ravikumar, B. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.9.1107 · Cited by 1,099 · see citing works
Luk, K. C., Kehm, V. M., Zhang, B., O’Brien, P., Trojanowski, J. Q., & Lee, V. M. ‐. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20112457 · Cited by 1,087 · see citing works
Self-citationGiasson, B. I., Murray, I. V. J., Trojanowski, J. Q., & Lee, V. M.-Y. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008919200 · Cited by 1,080 · see citing works
Self-citationOxidative stress and the pathogenesis of Parkinson's disease
Jenner, P., & Olanow, C. W. (1996) · Neurology · doi:10.1212/wnl.47.6_suppl_3.161s · Cited by 971 · see citing works
Luk, K. C., Song, C., O’Brien, P., Stieber, A., Branch, J. R., Brunden, K. R., Trojanowski, J. Q., & Lee, V. M. ‐. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908005106 · Cited by 958 · see citing works
Self-citationMisfolded proteins partition between two distinct quality control compartments
Kaganovich, D., Kopito, R., & Frydman, J. (2008) · Nature · doi:10.1038/nature07195 · Cited by 932 · see citing works
Autophagy gone awry in neurodegenerative diseases
Wong, E. S. P., & Cuervo, A. M. (2010) · Nature Neuroscience · doi:10.1038/nn.2575 · Cited by 883 · see citing works
The cell biology of lysosomal storage disorders
Futerman, A., & van Meer, G. (2004) · Nature reviews. Molecular cell biology · doi:10.1038/nrm1423 · Cited by 836 · see citing works
α-Synuclein impairs macroautophagy: implications for Parkinson’s disease
Winslow, A. R., Chen, C.-W., Corrochano, S., Acevedo-Arozena, A., Gordon, D. E., Peden, A. A., Lichtenberg, M., Menzies, F. M., Ravikumar, B., Imarisio, S., et al. (2010) · Journal of Cell Biology · doi:10.1083/jcb.201003122 · Cited by 825 · see citing works
Prion-like transmission of protein aggregates in neurodegenerative diseases
Brundin, P., Melki, R., & Kopito, R. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2873 · Cited by 778 · see citing works
Methods for Monitoring Autophagy from Yeast to Human
Klionsky, D. J., Cuervo, A. M., & Seglen, P. O. (2007) · Autophagy · doi:10.4161/auto.3678 · Cited by 656 · see citing works
Dopamine-modified α-synuclein blocks chaperone-mediated autophagy
Martínez‐Vicente, M., Tallóczy, Z., Kaushik, S., Massey, A. C., Mazzulli, J. R., Mosharov, E. V., Hodara, R., Fredenburg, R. A., Wu, D.-C., Follenzi, A., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci32806 · Cited by 633 · see citing works
Maturation of Autophagic Vacuoles in Mammalian Cells
Eskelinen, E.-L. (2005) · Autophagy · doi:10.4161/auto.1.1.1270 · Cited by 626 · see citing works
p62 Is a Common Component of Cytoplasmic Inclusions in Protein Aggregation Diseases
Zatloukal, K., Stumptner, C., Fuchsbichler, A., Heid, H., Schnoelzer, M., Kenner, L., Kleinert, R., Prinz, M., Aguzzi, A., & Denk, H. (2002) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64369-6 · Cited by 624 · see citing works
The mitochondrial permeability transition initiates autophagy in rat hepatocytes
Elmore, S. P., Qian, T., Grissom, S. F., & Lemasters, J. J. (2001) · The FASEB Journal · doi:10.1096/fj.01-0206fje · Cited by 607 · see citing works
Sarkar, S., Ravikumar, B., Floto, R. A., & Rubinsztein, D. C. (2009) · Cell Death & Differentiation · doi:10.1038/cdd.2008.110 · Cited by 578 · see citing works
Lysosomal membrane glycoproteins. Structure, biosynthesis, and intracellular trafficking.
Fukuda, M. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)54636-6 · Cited by 561 · see citing works
In search of an “autophagomometer”
Rubinsztein, D. C., Cuervo, A. M., Ravikumar, B., Sarkar, S., Korolchuk, V. I., Kaushik, S., & Klionsky, D. J. (2009) · Autophagy · doi:10.4161/auto.5.5.8823 · Cited by 551 · see citing works
An Atg4B Mutant Hampers the Lipidation of LC3 Paralogues and Causes Defects in Autophagosome Closure
Fujita, N., Hayashi, M., Fukumoto, H., Omori, H., Yamamoto, A., Noda, T., & Yoshimori, T. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-03-0312 · Cited by 527 · see citing works
The Parkinson's disease protein α-synuclein disrupts cellular Rab homeostasis
Gitler, A. D., Bevis, B. J., Shorter, J., Strathearn, K. E., Hamamichi, S., Su, L. J., Caldwell, K. A., Caldwell, G. A., Rochet, J., McCaffery, J. M., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710685105 · Cited by 527 · see citing works
Fighting neurodegeneration with rapamycin: mechanistic insights
Bové, J., Martínez‐Vicente, M., & Vila, M. (2011) · Nature reviews. Neuroscience · doi:10.1038/nrn3068 · Cited by 525 · see citing works
Wakabayashi, K., Tanji, K., Mori, F., & Takahashi, H. (2007) · Neuropathology · doi:10.1111/j.1440-1789.2007.00803.x · Cited by 516 · see citing works
Synphilin-1 associates with α-synuclein and promotes the formation of cytosolic inclusions
Engelender, S., Kaminsky, Z. A., Guo, X., Sharp, A. H., Amaravi, R. K., Kleiderlein, J. J., Margolis, R. L., Troncoso, J. C., Lanahan, A. A., Worley, P. F., et al. (1999) · Nature Genetics · doi:10.1038/8820 · Cited by 488 · see citing works
Galvin, J. E., Lee, V. M. ‐., & Trojanowski, J. Q. (2001) · Archives of Neurology · doi:10.1001/archneur.58.2.186 · Cited by 466 · see citing works
Self-citationIntracellular Protein Catabolism and its Control During Nutrient Deprivation and Supply
Mortimore, G. E., & Pösö, A. R. (1987) · Annual Review of Nutrition · doi:10.1146/annurev.nu.07.070187.002543 · Cited by 457 · see citing works
Induction of α-Synuclein Aggregation by Intracellular Nitrative Insult
Paxinou, E., Chen, Q., Weisse, M., Giasson, B. I., Norris, E. H., Rueter, S. M., Trojanowski, J. Q., Lee, V. M. ‐., & Ischiropoulos, H. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-20-08053.2001 · Cited by 440 · see citing works
Self-citationKuzuhara, S., Mori, H., Izumiyama, N., Yoshimura, M., & Ihara, Y. (1988) · Acta Neuropathologica · doi:10.1007/bf00687787 · Cited by 409 · see citing works
Oxidative Stress and Genetics in the Pathogenesis of Parkinson's Disease
Zhang, Y., Dawson, V. L., & Dawson, T. M. (2000) · Neurobiology of Disease · doi:10.1006/nbdi.2000.0319 · Cited by 406 · see citing works
Autophagy and other vacuolar protein degradation mechanisms
Seglen, P. O., & Bohley, P. (1992) · Cellular and Molecular Life Sciences · doi:10.1007/bf01923509 · Cited by 405 · see citing works
Ebrahimi‐Fakhari, D., Cantuti‐Castelvetri, I., Fan, Z., Rockenstein, E. M., Masliah, E., Hyman, B. T., McLean, P. J., & Unni, V. K. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.1560-11.2011 · Cited by 378 · see citing works
Zhang, X., Li, L., Chen, S., Yang, D., Wang, Y., Zhang, X., Wang, Z., & Le, W. (2011) · Autophagy · doi:10.4161/auto.7.4.14541 · Cited by 364 · see citing works
Neurodegenerative lysosomal disorders: A continuum from development to late age
Nixon, R. A., Yang, D.-S., & Lee, J.-H. (2008) · Autophagy · doi:10.4161/auto.6259 · Cited by 362 · see citing works
p62/SQSTM1: A Missing Link between Protein Aggregates and the Autophagy Machinery
Bjørkøy, G., Lamark, T., & Johansen, T. (2006) · Autophagy · doi:10.4161/auto.2.2.2405 · Cited by 322 · see citing works
Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP
Gómez‐Suaga, P., Luzón-Toro, B., Churamani, D., Zhang, L., Bloor-Young, D., Patel, S., Woodman, P. G., Churchill, G. C., & Hilfiker, S. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr481 · Cited by 312 · see citing works
Formation and Removal of α-Synuclein Aggregates in Cells Exposed to Mitochondrial Inhibitors
Lee, H.-J., Shin, S. Y., Choi, C., Lee, Y. H., & Lee, S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m105326200 · Cited by 293 · see citing works
Deficiency of ATP13A2 Leads to Lysosomal Dysfunction, α-Synuclein Accumulation, and Neurotoxicity
Usenovic, M., Tresse, E., Mazzulli, J. R., Taylor, J. P., & Krainc, D. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5575-11.2012 · Cited by 291 · see citing works
Are synucleinopathies prion-like disorders?
Angot, É., Steiner, J. A., Hansen, C., Li, J., & Brundin, P. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70213-1 · Cited by 283 · see citing works
The Parkinson-associated protein PINK1 interacts with Beclin1 and promotes autophagy
Michiorri, S., Gelmetti, V, Giarda, E., Lombardi, F., Romano, F., Marongiu, R., Nerini-Molteni, S., Sale, P., Vago, R., Arena, G., et al. (2010) · Cell Death & Differentiation · doi:10.1038/cdd.2009.200 · Cited by 260 · see citing works
McLean, P. J., Kawamata, H., & Hyman, B. T. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00113-0 · Cited by 236 · see citing works
Processing and activation of latent heparanase occurs in lysosomes
Zetser, A., Levy‐Adam, F., Cohen‐Kaplan, V., Gingis‐Velitski, S., Bashenko, Y., Schubert, S. Y., Flugelman, M. Y., Vlodavsky, I., & Ilan, N. (2004) · Journal of Cell Science · doi:10.1242/jcs.01068 · Cited by 218 · see citing works
Ii, K., Ito, H., Tanaka, K., & Hirano, A. (1997) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199702000-00002 · Cited by 215 · see citing works
Bartlett, B. J., Isakson, P., Lewerenz, J., Sanchez, H., Kotzebue, R. W., Cumming, R. C., Harris, G. L., Nezis, I. P., Schubert, D. R., Simonsen, A., et al. (2011) · Autophagy · doi:10.4161/auto.7.6.14943 · Cited by 215 · see citing works
Autophagosome-Lysosome Fusion Depends on the pH in Acidic Compartments in CHO Cells
Kawai, A., Uchiyama, H., Takano, S., Nakamura, N., & Ohkuma, S. (2007) · Autophagy · doi:10.4161/auto.3634 · Cited by 205 · see citing works
Autophagy-mediated clearance of aggresomes is not a universal phenomenon
Wong, E. S. P., Tan, J. M. M., Soong, W.-E., Hussein, K., Nukina, N., Dawson, V. L., Dawson, T. M., Cuervo, A. M., & Lim, K. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn157 · Cited by 157 · see citing works
A rapid cellular FRET assay of polyglutamine aggregation identifies a novel inhibitor
Pollitt, S. K., Pallos, J., Shao, J., Desai, U. A., Ma, A. A. K., Thompson, L. M., Marsh, J. L., & Diamond, M. I. (2003) · Neuron · doi:10.1016/s0896-6273(03)00697-4 · Cited by 151 · see citing works
Young, J. E., Martinez, R. A., & Spada, A. R. L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806088200 · Cited by 129 · see citing works
Lee, J., & Gao, F. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0924-09.2009 · Cited by 124 · see citing works
Protein Folding, Misfolding, and Aggregation. Formation of Inclusion Bodies and Aggresomes
Markossian, K. A., & Kurganov, B. I. (2004) · Biochemistry (Moscow) · doi:10.1023/b:biry.0000043539.07961.4c · Cited by 123 · see citing works
p62/SQSTM1-Dependent Autophagy of Lewy Body-Like α-Synuclein Inclusions
Watanabe, Y., Tatebe, H., Taguchi, K., Endo, Y., Tokuda, T., Mizuno, T., Nakagawa, M., & Tanaka, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052868 · Cited by 99 · see citing works
Structural Aspects of Autophagy
Seglen, P. O., Berg, T. O., Blankson, H., Fengsrud, M., Holen, I., & STRØMHAUG, P. E. (1996) · Advances in experimental medicine and biology · doi:10.1007/978-1-4613-0335-0_12 · Cited by 91 · see citing works
Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are α-synucleinopathies
Spillantini, M. G. (1999) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(99)00031-0 · Cited by 80 · see citing works
Soper, J. H., Kehm, V. M., Burd, C. G., Bankaitis, V. A., & Lee, V. M. ‐. (2010) · Journal of Molecular Neuroscience · doi:10.1007/s12031-010-9455-5 · Cited by 73 · see citing works
Self-citationMortimore, G. E., Miotto, G., Venerando, R., & Kadowaki, M. (1996) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-1-4615-5833-0_4 · Cited by 73 · see citing works
Parkinson's disease involves autophagy and abnormal distribution of cathepsin L
Li, L., Wang, X., Fei, X., Xia, L., Qin, Z., & Liang, Z. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.11.068 · Cited by 68 · see citing works
Higashi, S., Moore, D. J., Minegishi, M., Kasanuki, K., Fujishiro, H., Kabuta, T., Togo, T., Katsuse, O., Uchikado, H., Furukawa, Y., et al. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318211c86a · Cited by 61 · see citing works
Zagranichnaya, T. K., Wu, X., Danos, A. M., & Villereal, M. L. (2004) · Physiological Genomics · doi:10.1152/physiolgenomics.00099.2004 · Cited by 32 · see citing works
In Vivo Spreading of Tau Pathology
Soto, C. A. (2012) · Neuron · doi:10.1016/j.neuron.2012.02.006 · Cited by 29 · see citing works
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Poewe, W., Seppi, K., Tanner, C. M., Halliday, G. M., Brundin, P., Volkmann, J., Schrag, A.-E., & Lang, A. E. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.13 · Cited by 5,415 · see citing works
mTOR at the nexus of nutrition, growth, ageing and disease
Liu, G. Y., & Sabatini, D. M. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0199-y · Cited by 2,737 · see citing works
Proteasomal and Autophagic Degradation Systems
Đikić, I. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061516-044908 · Cited by 1,165 · see citing works
Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities
Menzies, F. M., Fleming, A., Caricasole, A., Bento, C. F., Andrews, S. P., Ashkenazi, A., Füllgrabe, J., Jackson, A., Jimenez Sanchez, M., Karabiyik, C., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.01.022 · Cited by 1,134 · see citing works
α-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies
Wong, Y. C., & Krainc, D. (2017) · Nature Medicine · doi:10.1038/nm.4269 · Cited by 897 · see citing works
Mahul-Mellier, A.-L., Burtscher, J., Maharjan, N., Weerens, L., Croisier, M., Kuttler, F., Leleu, M., Knott, G. W., & Lashuel, H. A. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1913904117 · Cited by 710 · see citing works
Volpicelli-Daley, L. A., Luk, K. C., & Lee, V. M.-Y. (2014) · Nature Protocols · doi:10.1038/nprot.2014.143 · Cited by 731 · see citing works
Self-citationCell-to-cell transmission of pathogenic proteins in neurodegenerative diseases
Guo, J. L., & Lee, V. M. Y. (2014) · Nature Medicine · doi:10.1038/nm.3457 · Cited by 641 · see citing works
Self-citationDehay, B., Bourdenx, M., Gorry, P., Przedborski, S., Vila, M., Hunot, S., Singleton, A., Olanow, C. W., Merchant, K., Bézard, E., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)00006-x · Cited by 530 · see citing works
The different autophagy degradation pathways and neurodegeneration
Fleming, A., Bourdenx, M., Fujimaki, M., Karabiyik, C., Krause, G. J., Lopez, A., Martín‐Segura, A., Puri, C., Scrivo, A., Skidmore, J., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.01.017 · Cited by 485 · see citing works
Tunneling nanotubes spread fibrillar α-synuclein by intercellular trafficking of lysosomes
Abounit, S., Bousset, L., Loria, F., Zhu, S., de Chaumont, F., Pieri, L., Olivo‐Marin, J., Melki, R., & Zurzolo, C. (2016) · The EMBO Journal · doi:10.15252/embj.201593411 · Cited by 414 · see citing works
Like prions: the propagation of aggregated tau and α-synuclein in neurodegeneration
Goedert, M., Masuda-Suzukake, M., & Falcon, B. (2017) · Brain · doi:10.1093/brain/aww230 · Cited by 323 · see citing works
Therapeutic potential of autophagy-enhancing agents in Parkinson’s disease
Moors, T. E., Hoozemans, J. J. M., Ingrassia, A. M. T., Beccari, T., Parnetti, L., Chartier‐Harlin, M., & van de Berg, W. D. J. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0154-3 · Cited by 279 · see citing works
Autophagy and A lpha‐ S ynuclein: R elevance to P arkinson's D isease and R elated S ynucleopathies
Xilouri, M., Brekk, O. R., & Stefanis, L. (2016) · Movement Disorders · doi:10.1002/mds.26477 · Cited by 266 · see citing works
Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins
Flavin, W. P., Bousset, L., Green, Z. C., Chu, Y., Skarpathiotis, S., Chaney, M. J., Kordower, J. H., Melki, R., & Campbell, E. M. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1722-x · Cited by 254 · see citing works
Bassil, F., Brown, H. J., Pattabhiraman, S., Iwasyk, J. E., Maghames, C. M., Meymand, E. S., Cox, T. O., Riddle, D. M., Zhang, B., Trojanowski, J. Q., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.10.010 · Cited by 243 · see citing works
Self-citationLoss of Mitochondrial Function Impairs Lysosomes
Demers-Lamarche, J., Guillebaud, G., Tlili, M., Todkar, K. J., Bélanger, N., Grondin, M., Nguyen, A., Michel, J. J. C., & Germain, M. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.695825 · Cited by 242 · see citing works
Autophagy Induction as a Therapeutic Strategy for Neurodegenerative Diseases
Djajadikerta, A., Keshri, S., Tanasa, M. P., Prestil, R., Ryan, L., & Rubinsztein, D. C. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.12.035 · Cited by 238 · see citing works
Volpicelli‐Daley, L. A., Gamble, K. L., Schultheiss, C. E., Riddle, D. M., West, A. B., & Lee, V. M. ‐. (2014) · Molecular Biology of the Cell · doi:10.1091/mbc.e14-02-0741 · Cited by 233 · see citing works
Self-citationGrassi, D., Howard, S., Zhou, M., Diaz-Perez, N., Urban, N. T., Guerrero-Given, D., Kamasawa, N., Volpicelli-Daley, L. A., LoGrasso, P., & Lasmézas, C. I. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1713849115 · Cited by 228 · see citing works
Self-citationStructure, function and toxicity of alpha‐synuclein: the Bermuda triangle in synucleinopathies
Villar‐Piqué, A., da Fonseca, T. L., & Outeiro, T. F. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13249 · Cited by 226 · see citing works
Seeking a Mechanism for the Toxicity of Oligomeric α-Synuclein
Hall‐Roberts, H., & Brown, D. R. (2015) · Biomolecules · doi:10.3390/biom5020282 · Cited by 213 · see citing works
ER stress and impaired autophagy flux in neuronal degeneration and brain injury
Yin, Y., Sun, G., Li, E., Kiselyov, K. I., & Sun, D. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.08.008 · Cited by 212 · see citing works
Autophagy in Neurodegenerative Diseases: A Hunter for Aggregates
Park, H., Kang, J., & Lee, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093369 · Cited by 209 · see citing works
Autophagy and Its Normal and Pathogenic States in the Brain
Yamamoto, A., & Yue, Z. (2014) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071013-014149 · Cited by 204 · see citing works
Bourdenx, M., Koulakiotis, N. S., Sanoudou, D., Bézard, E., Dehay, B., & Tsarbopoulos, A. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.07.003 · Cited by 189 · see citing works
Accumulation of autophagosomes confers cytotoxicity
Button, R. W., Roberts, S. L., Willis, T. L., Hanemann, C. O., & Luo, S. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.782276 · Cited by 177 · see citing works
Mitochondrial dynamics in Parkinson's disease: a role for α-synuclein?
Devoto, V. M. P., & Falzone, T. L. (2017) · Disease Models & Mechanisms · doi:10.1242/dmm.026294 · Cited by 180 · see citing works
The 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 173 · see citing works
How is alpha‐synuclein cleared from the cell?
Stefanis, L., Emmanouilidou, E., Pantazopoulou, M., Kirik, D., Vekrellis, K., & Tofaris, G. K. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14704 · Cited by 174 · see citing works
Lysosomal Dysfunction and α‐Synuclein Aggregation in Parkinson's Disease: Diagnostic Links
Moors, T. E., Paciotti, S., Chiasserini, D., Calabresi, P., Parnetti, L., Beccari, T., & van de Berg, W. D. J. (2016) · Movement Disorders · doi:10.1002/mds.26562 · Cited by 175 · see citing works
Emerging degrader technologies engaging lysosomal pathways
Ding, Y., Xing, D., Fei, Y., & Lu, B. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00624c · Cited by 162 · see citing works
Alpha-Synuclein: From Early Synaptic Dysfunction to Neurodegeneration
Ghiglieri, V., Calabrese, V., & Calabresi, P. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00295 · Cited by 158 · see citing works
Cellular proteostasis: degradation of misfolded proteins by lysosomes
Jackson, M. P., & Hewitt, E. W. (2016) · Essays in Biochemistry · doi:10.1042/ebc20160005 · Cited by 155 · see citing works
Tenreiro, 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 147 · see citing works
Glucocerebrosidase Activity Modulates Neuronal Susceptibility to Pathological α-Synuclein Insult
Henderson, M. X., Sedor, S. F., McGeary, I., Cornblath, E. J., Peng, C., Riddle, D. M., Li, H. L., Zhang, B., Brown, H. J., Olufemi, M. F., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.12.004 · Cited by 147 · see citing works
Self-citationDisruption 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 143 · see citing works
Pinnell, J. R., Cui, M., & Tieu, K. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15288 · Cited by 144 · see citing works
Autophagy impairment in Parkinson’s disease
Karabiyik, C., Lee, M. J., & Rubinsztein, D. C. (2017) · Essays in Biochemistry · doi:10.1042/ebc20170023 · Cited by 137 · see citing works
Loss of autophagy in dopaminergic neurons causes Lewy pathology and motor dysfunction in aged mice
Sato, S., Uchihara, T., Fukuda, T., Noda, S., Kondo, H., Saiki, S., Komatsu, M., Uchiyama, Y., Tanaka, K., & Hattori, N. (2018) · Scientific Reports · doi:10.1038/s41598-018-21325-w · Cited by 125 · see citing works
Prion-Like Mechanisms in Parkinson’s Disease
Ma, J., Gao, J., Wang, J., & Xie, A. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00552 · Cited by 124 · see citing works
Neuronal vulnerability in Parkinson disease: Should the focus be on axons and synaptic terminals?
Wong, Y. C., Luk, K. C., Purtell, K., Burke, S., Stoessl, A. J., Trudeau, L., Yue, Z., Krainc, D., Oertel, W. H., Obeso, J. A., et al. (2019) · Movement Disorders · doi:10.1002/mds.27823 · Cited by 123 · see citing works
Self-citationAutophagosome dynamics in neurodegeneration at a glance
Wong, Y. C., & Holzbaur, E. L. F. (2015) · Journal of Cell Science · doi:10.1242/jcs.161216 · Cited by 116 · see citing works
Ganesan, D., & Cai, Q. (2021) · Biochemical Journal · doi:10.1042/bcj20200917 · Cited by 114 · see citing works
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 116 · see citing works
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 114 · see citing works
Circadian clocks and neurodegenerative diseases: time to aggregate?
Hastings, M. H., & Goedert, M. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.05.004 · Cited by 114 · see citing works
α-Synuclein modulates tau spreading in mouse brains
Bassil, F., Meymand, E. S., Brown, H. J., Xu, H. W., Cox, T. O., Pattabhiraman, S., Maghames, C. M., Wu, Q., Zhang, B., Trojanowski, J. Q., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20192193 · Cited by 111 · see citing works
Self-citationYuan, 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 · see citing works
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 110 · see citing works
Kim, S., Jung, U. J., & Kim, S. R. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14020386 · Cited by 123 · see citing works
The Endolysosomal System and Proteostasis: From Development to Degeneration
Winckler, B., Faúndez, V., Maday, S., Cai, Q., Almeida, C. G., & Zhang, H. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1665-18.2018 · Cited by 105 · see citing works
Dysregulation of autophagy and mitochondrial function in Parkinson’s disease
Wang, B., Abraham, N. A., Gao, G., & Yang, Q. (2016) · Translational Neurodegeneration · doi:10.1186/s40035-016-0065-1 · Cited by 106 · see citing works
Alpha-Synuclein Targeting Therapeutics for Parkinson's Disease and Related Synucleinopathies
Menon, S. A., Armstrong, S. E. M., Hamzeh, A. M., Visanji, N. P., Sardi, S. P., & Tandon, A. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.852003 · Cited by 107 · see citing works
Transmission of α-synuclein seeds in neurodegenerative disease: recent developments
Karpowicz, R. J., Trojanowski, J. Q., & Lee, V. M. ‐. (2019) · Laboratory Investigation · doi:10.1038/s41374-019-0195-z · Cited by 102 · see citing works
Self-citationSorting out release, uptake and processing of alpha‐synuclein during prion‐like spread of pathology
Tyson, T., Steiner, J. A., & Brundin, P. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13449 · Cited by 102 · see citing works
Therapeutics in the Pipeline Targeting α-Synuclein for Parkinson's Disease
Jasutkar, H. G., Oh, S. E., & Mouradian, M. M. (2022) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000133 · Cited by 102 · see citing works
Mitophagy in neurodegenerative diseases
Rodolfo, C., Campello, S., & Cecconi, F. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.08.004 · Cited by 100 · see citing works
Obergasteiger, J., Frapporti, G., Pramstaller, P. P., Hicks, A. A., & Volta, M. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0273-5 · Cited by 98 · see citing works
Key genes and convergent pathogenic mechanisms in Parkinson disease
Coukos, R., & Krainc, D. (2024) · Nature reviews. Neuroscience · doi:10.1038/s41583-024-00812-2 · Cited by 102 · see citing works
Import and Export of Misfolded α-Synuclein
Rodriguez, L., Marano, M. M., & Tandon, A. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00344 · Cited by 93 · see citing works
Neuroinflammation in Multiple System Atrophy: Response to and Cause of α-Synuclein Aggregation
Vieira, B. D. M., Radford, R. A., Chung, R. S., Guillemin, G. J., & Pountney, D. L. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00437 · Cited by 93 · see citing works
ErbB2 regulates autophagic flux to modulate the proteostasis of APP-CTFs in Alzheimer’s disease
Wang, B.-J., Her, G. M., Hu, M., Chen, Y.-W., Tung, Y.-T., Wu, P., Hsu, W., Lee, H., Jin, L., Hwang, S. L., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1618804114 · Cited by 92 · see citing works
Redmann, M., Darley-Usmar, V. M., & Zhang, J. (2016) · Aging and Disease · doi:10.14336/ad.2015.0820 · Cited by 92 · see citing works
The endosomal pathway in Parkinson's disease
Perrett, R. M., Alexopoulou, Z., & Tofaris, G. K. (2015) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2015.02.009 · Cited by 87 · see citing works
α-Synuclein fibril-induced paradoxical structural and functional defects in hippocampal neurons
Froula, J. M., Henderson, B. W., Gonzalez, J., Vaden, J. H., Mclean, J. W., Wu, Y., Banumurthy, G., Overstreet‐Wadiche, L., Herskowitz, J. H., & Volpicelli‐Daley, L. A. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0537-x · Cited by 89 · see citing works
Self-citationLuan, Y.-N., Ren, X., Zheng, W., Zeng, Z., Guo, Y., Hou, Z., Guo, W., Chen, X., Li, F., & Chen, J.-F. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00301 · Cited by 76 · see citing works
Pathogenesis of α-Synuclein in Parkinson’s Disease: From a Neuron-Glia Crosstalk Perspective
Yi, S., Wang, L., Wang, H., Ho, M. S.-C., & Zhang, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232314753 · Cited by 90 · see citing works
RISC in PD: the impact of microRNAs in Parkinson's disease cellular and molecular pathogenesis
Heman-Ackah, S. M., Hallegger, M., Rao, M. S., & Wood, M. J. A. (2013) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2013.00040 · Cited by 83 · see citing works
α-Synuclein interacts with the switch region of Rab8a in a Ser129 phosphorylation-dependent manner
Yin, G., da Fonseca, T. L., Eisbach, S. E., Anduaga, A. M., Breda, C., Orcellet, M. L., Szegő, É. M., Guerreiro, P. S., Lázaro, D. F., Braus, G. H., et al. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.06.018 · Cited by 84 · see citing works
Autophagy in Synucleinopathy: The Overwhelmed and Defective Machinery
Arotçarena, M.-L., Teil, M., & Dehay, B. (2019) · Cells · doi:10.3390/cells8060565 · Cited by 85 · see citing works
Yu, Y., Feng, L., Li, J., Lan, X., Lixiang, A., Lv, X., Zhang, M., & Chen, L. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.07.003 · Cited by 82 · see citing works
Preserving Lysosomal Function in the Aging Brain: Insights from Neurodegeneration
Peng, W., Minakaki, G., Nguyen, M., & Krainc, D. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00742-3 · Cited by 79 · see citing works
The Dynamics and Turnover of Tau Aggregates in Cultured Cells
Guo, J., Buist, A., Soares, A. C., Callaerts, K., Calafate, S., Stevenaert, F., Daniels, J. P., Zoll, B. E., Crowe, A., Brunden, K. R., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.712083 · Cited by 80 · see citing works
Self-citationFollett, J., Bugarc̀ić, A., Yang, Z., Ariotti, N., Norwood, S. J., Collins, B. M., Parton, R. G., & Teasdale, R. D. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.703157 · Cited by 81 · see citing works
α-synuclein impairs autophagosome maturation through abnormal actin stabilization
Sarkar, S., Olsen, A. L., Sygnecka, K., Lohr, K. M., & Feany, M. Β. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009359 · Cited by 79 · see citing works
Alpha-Synuclein as a Prominent Actor in the Inflammatory Synaptopathy of Parkinson’s Disease
Cardinale, A., Calabrese, V., de Iure, A., & Picconi, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126517 · Cited by 77 · see citing works
Yan, M., Xiong, M., Dai, L., Zhang, X., Zha, Y., Deng, X., Yu, Z., & Zhang, Z. (2022) · npj Parkinson s Disease · doi:10.1038/s41531-021-00272-w · Cited by 78 · see citing works
Ma, L., Yang, C., Zhang, X., Li, Y., Wang, S. L., Zheng, L., & Huang, K. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.10.003 · Cited by 77 · see citing works
Lin, K.-L., Lin, K.-J., Wang, P., Chuang, J., Lin, H., Chen, S., Chuang, Y., Huang, S., Tiao, M., Chen, J., et al. (2018) · Free Radical Research · doi:10.1080/10715762.2018.1489128 · Cited by 78 · see citing works
(Poly)phenols protect from α-synuclein toxicity by reducing oxidative stress and promoting autophagy
Macedo, D., Tavares, L., McDougall, G. J., Miranda, H. V., Stewart, D., Ferreira, R. B., Tenreiro, S., Outeiro, T. F., & dos Santos, C. N. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu585 · Cited by 76 · see citing works
Common Mechanisms Underlying α-Synuclein-Induced Mitochondrial Dysfunction in Parkinson’s Disease
Sohrabi, T., Mirzaei-Behbahani, B., Zadali, R., Pirhaghi, M., Morozova‐Roche, L. A., & Meratan, A. A. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.167992 · Cited by 78 · see citing works
Mechanisms of alpha-synuclein toxicity: An update and outlook
Brás, I. C., Xylaki, M., & Outeiro, T. F. (2019) · Progress in brain research · doi:10.1016/bs.pbr.2019.10.005 · Cited by 73 · see citing works
Pathogenic Ubqln2 gains toxic properties to induce neuron death
Wu, Q., Liu, M., Huang, C., Liu, X., Huang, B., Li, N., Zhou, H., & Xia, X. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1367-y · Cited by 75 · see citing works
Autophagy in Astrocytes and its Implications in Neurodegeneration
Sung, K., & Jiménez-Sánchez, M. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.12.041 · Cited by 74 · see citing works
Wang, T., & Hay, J. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00433 · Cited by 73 · see citing works
Defective Autophagy in Parkinson’s Disease: Lessons from Genetics
Zhang, H., Duan, C., & Yang, H. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8787-5 · Cited by 72 · see citing works
Regulation of neuronal autophagy and the implications in neurodegenerative diseases
Cai, Q., & Ganesan, D. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105582 · Cited by 67 · see citing works
Targeting the Autophagy/Lysosomal Degradation Pathway in Parkinsons Disease
Rivero-Ríos, P., Madero-Pérez, Fernández, B., & Hilfiker, S. (2016) · Current Neuropharmacology · doi:10.2174/1570159x13666151030103027 · Cited by 69 · see citing works
Teves, J. M., Bhargava, V., Kirwan, K. R., Corenblum, M. J., Justiniano, R., Wondrak, G. T., Anandhan, A., Flores, A. J., Schipper, D. A., Khalpey, Z. I., et al. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00737 · Cited by 68 · see citing works
Tsujimura, A., Taguchi, K., Watanabe, Y., Tatebe, H., Tokuda, T., Mizuno, T., & Tanaka, M. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.10.011 · Cited by 67 · see citing works
Wang, X., Feng, S., Wang, Y., Yuan, Y., Li, Z., Chen, N., Wang, Z., & Zhang, Y. (2021) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-021-01039-w · Cited by 64 · see citing works
The Emerging Roles of Autophagy in Human Diseases
Lei, Y., & Klionsky, D. J. (2021) · Biomedicines · doi:10.3390/biomedicines9111651 · Cited by 66 · see citing works
The Hidden Cell-to-Cell Trail of α-Synuclein Aggregates
Neupane, S., Cecco, E. D., & Aguzzi, A. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167930 · Cited by 67 · see citing works
Found in Translation: The Utility of C. elegans Alpha-Synuclein Models of Parkinson’s Disease
Gaeta, A. L., Caldwell, K. A., & Caldwell, G. A. (2019) · Brain Sciences · doi:10.3390/brainsci9040073 · Cited by 70 · see citing works
Mallucci, G. R., Klenerman, D., & Rubinsztein, D. C. (2020) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-040320-120625 · Cited by 62 · see citing works
Achour, I., Arel-Dubeau, A.-M., Renaud, J., Legrand, M., Attard, E., Germain, M., & Martinoli, M. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17081293 · Cited by 64 · see citing works
miR-124 downregulates BACE 1 and alters autophagy in APP/PS1 transgenic mice
Du, X., Huo, X., Yang, Y., Hu, Z., Botchway, B. O. A., Jiang, Y., & Fang, M. (2017) · Toxicology Letters · doi:10.1016/j.toxlet.2017.08.082 · Cited by 63 · see citing works
Lashuel, H. A., Mahul‐Mellier, A., Novello, S., Hegde, R. N., Jasiqi, Y., Altay, M. F., Donzelli, S., DeGuire, S. M., Burai, R., Magalhães, P., et al. (2022) · npj Parkinson s Disease · doi:10.1038/s41531-022-00388-7 · Cited by 61 · see citing works
Inhibition of HDAC6 activity protects dopaminergic neurons from alpha-synuclein toxicity
Francelle, L., Outeiro, T. F., & Rappold, G. (2020) · Scientific Reports · doi:10.1038/s41598-020-62678-5 · Cited by 60 · see citing works
- Authors
- Tanik, S. A., Schultheiss, C. E., Volpicelli-Daley, L. A., Brunden, K. R., & Lee, V. M. Y.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Lee, Virginia M.Y.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 288
- Issue
- 21
- Pages
- 15194-15210
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3663539
- OpenAlex
- W2017642230
- Cited by
- 326
- References
- 83
- Citations by year
- 2026: 17 · 2025: 23 · 2024: 25 · 2023: 11 · 2022: 27 · 2021: 28 · 2020: 40 · 2019: 40 · 2018: 28 · 2017: 26 · 2016: 23 · 2015: 18 · 2014: 15 · 2013: 5
- FWCI
- 12.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cedars-Sinai Medical Center
- National Institutes of Health (NS053488)
- National Institute of Neurological Disorders and Stroke (NS053488, P50NS053488)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- alpha-synuclein, Lewy bodies, macroautophagy, autophagosome maturation, Parkinson's disease, neurodegeneration, proteasomal degradation, autophagy dysfunction, neuronal cell death
- MeSH terms
- Animals, Autophagy, HeLa Cells, Humans, Models, Biological, Neurons, Parkinson Disease, Lewy Bodies, Proteasome Endopeptidase Complex, Mice, alpha-Synuclein, HEK293 Cells, Proteolysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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