Inclusion formation and neuronal cell death through neuron-to-neuron transmission of α-synuclein
Open accessAbstract
Neuronal accumulation of alpha-synuclein and Lewy body formation are characteristic to many neurodegenerative diseases, including Parkinson's disease (PD). This Lewy pathology appears to spread throughout the brain as the disease progresses. Furthermore, recent studies showed the occurrence of Lewy pathology in neurons grafted into the brains of PD patients, suggesting the spread of pathology from the host tissues to the grafts. The mechanism underlying this propagation is unknown. Here, we show that alpha-synuclein is transmitted via endocytosis to neighboring neurons and neuronal precursor cells, forming Lewy-like inclusions. Moreover, alpha-synuclein was transmitted from the affected neurons to engrafted neuronal precursor cells in a transgenic model of PD-like pathology. Failure of the protein quality control systems, especially lysosomes, promoted the accumulation of transmitted alpha-synuclein and inclusion formation. Cells exposed to neuron-derived alpha-synuclein showed signs of apoptosis, such as nuclear fragmentation and caspase 3 activation, both in vitro and in vivo. These findings demonstrate the cell-to-cell transmission of alpha-synuclein aggregates and provide critical insights into the mechanism of pathological progression in PD and other proteinopathies.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In cell culture, the prion-like propagation of α-synuclein lesions has been demonstrated.
“In cell culture, however, the prion-like propagation of α-synuclein lesions has been demonstrated80, 81”
From Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders (2011) · cites this paper as [80]
Alpha-synuclein is transmitted via endocytosis to neighboring neurons in vitro and in vivo.
“Others have shown in vitro and in vivo that alpha-synuclein is transmitted via endocytosis to neighboring neurons (Angot et al., 2012;Desplats et al., 2009).”
From The Gut-Brain Axis in Parkinson’s Disease: Possibilities for Food-Based Therapies (2017) · cites this paper as Desplats et al., 2009
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Staging of brain pathology related to sporadic Parkinson’s disease
Braak, H., Tredici, K. D., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00065-9 · Cited by 10,777 · see citing works
Dauer, W., & Przedborski, S. (2003) · Neuron · doi:10.1016/s0896-6273(03)00568-3 · Cited by 5,469 · see citing works
Spillantini, M. G., Crowther, R. A., Jakes, R., Hasegawa, M., & Goedert, M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6469 · Cited by 3,151 · see citing works
Li, J.-Y., Englund, E., Holton, J. L., Soulet, D., Hagell, P., Lees, A. J., Lashley, T., Quinn, N. P., Rehncrona, S., Björklund, A., et al. (2008) · Nature Medicine · doi:10.1038/nm1746 · Cited by 1,845 · see citing works
Lewy body–like pathology in long-term embryonic nigral transplants in Parkinson's disease
Kordower, J. H., Chu, Y., Hauser, R. A., Freeman, T. B., & Olanow, C. W. (2008) · Nature Medicine · doi:10.1038/nm1747 · Cited by 1,722 · see citing works
Molecular Pathways of Neurodegeneration in Parkinson's Disease
Dawson, T. M., & Dawson, V. L. (2003) · Science · doi:10.1126/science.1087753 · Cited by 1,659 · see citing works
Neuropathology of Parkinson's Disease
Forno, L. (1996) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199603000-00001 · Cited by 1,556 · see citing works
Propagation of Tau Misfolding from the Outside to the Inside of a Cell
Frost, B., Jacks, R. L., & Diamond, M. I. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808759200 · Cited by 1,252 · see citing works
Ramirez, A., Heimbach, A., Gründemann, J., Stiller, B., Hampshire, D., Cid, L. P., Goebel, I., Mubaidin, A. F., Wriekat, A.-L., Roeper, J., et al. (2006) · Nature Genetics · doi:10.1038/ng1884 · Cited by 1,208 · see citing works
Exogenous Induction of Cerebral ß-Amyloidogenesis Is Governed by Agent and Host
Meyer-Luehmann, M., Coomaraswamy, J., Bolmont, T., Kaeser, S., Schaefer, C., Kilger, E., Neuenschwander, A., Abramowski, D., Frey, P., Jaton, A. L., et al. (2006) · Science · doi:10.1126/science.1131864 · Cited by 971 · see citing works
Parkinson's disease: from monogenic forms to genetic susceptibility factors
Lesage, S., & Brice, A. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp012 · Cited by 946 · 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
Intravesicular Localization and Exocytosis of α-Synuclein and its Aggregates
Lee, H.-J., Patel, S. S., & Lee, S. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.0692-05.2005 · Cited by 798 · see citing works
Self-citationTHE BIOCHEMISTRY OF PARKINSON'S DISEASE
Cookson, M. (2005) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.082803.133400 · Cited by 659 · see citing works
The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease
Pan, T., Kondo, S., Le, W., & Jankovic, J. J. (2008) · Brain · doi:10.1093/brain/awm318 · Cited by 546 · see citing works
Gitler, A. D., Chesi, A., Geddie, M. L., Strathearn, K. E., Hamamichi, S., Hill, K. J., Caldwell, K. A., Caldwell, G. A., Cooper, A. A., Rochet, J., et al. (2009) · Nature Genetics · doi:10.1038/ng.300 · Cited by 535 · see citing works
Rockenstein, E., Mallory, M., Hashimoto, M., Song, D., Shults, C. W., Lang, I., & Masliah, E. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10231 · Cited by 502 · see citing works
Self-citationAssembly-dependent endocytosis and clearance of extracellular a-synuclein
Lee, H.-J., Suk, J.-E., Bae, E.-J., Lee, J.-H., Paik, S. R., & Lee, S.-J. (2008) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2008.01.017 · Cited by 470 · see citing works
Self-citationClearance of α-Synuclein Oligomeric Intermediates via the Lysosomal Degradation Pathway
Lee, H.-J., Khoshaghideh, F., Patel, S., & Lee, S.-J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.3809-03.2004 · Cited by 445 · see citing works
Self-citationMendez, I. M., Viñuela, Á., Astradsson, A., Mukhida, K., Hallett, P. J., Robertson, H. A., Tierney, T. S., Holness, R. O., Dagher, A., Trojanowski, J. Q., et al. (2008) · Nature Medicine · doi:10.1038/nm1752 · Cited by 442 · see citing works
Cytoplasmic penetration and persistent infection of mammalian cells by polyglutamine aggregates
Ren, P.-H., Lauckner, J. E., Kachirskaia, I., Heuser, J. E., Melki, R., & Kopito, R. R. (2009) · Nature Cell Biology · doi:10.1038/ncb1830 · Cited by 410 · see citing works
The role of α-synuclein in Parkinson's disease: insights from animal models
Lad, E. M., Dass, B., Collier, T. J., Kordower, J. H., & Steece‐Collier, K. (2003) · Nature reviews. Neuroscience · doi:10.1038/nrn1199 · Cited by 349 · see citing works
Clearance and deposition of extracellular α-synuclein aggregates in microglia
Lee, H.-J., Suk, J.-E., Bae, E.-J., & Lee, S.-J. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.05.045 · Cited by 343 · see citing works
Self-citationResearch in motion: the enigma of Parkinson's disease pathology spread
Brundin, P., Li, J., Holton, J. L., Lindvall, O., & Révész, T. (2008) · Nature reviews. Neuroscience · doi:10.1038/nrn2477 · Cited by 328 · 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
Self-citationTransplanted dopaminergic neurons develop PD pathologic changes: A second case report
Kordower, J. H., Chu, Y., Hauser, R. A., Olanow, C. W., & Freeman, T. B. (2008) · Movement Disorders · doi:10.1002/mds.22369 · Cited by 286 · see citing works
The neuropathogenic contributions of lysosomal dysfunction
Bahr, B. A., & Bendiske, J. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01192.x · Cited by 180 · see citing works
Origins and Effects of Extracellular α-synuclein: Implications in Parkinson’s Disease
Lee, S. (2007) · Journal of Molecular Neuroscience · doi:10.1007/s12031-007-0012-9 · Cited by 159 · see citing works
Self-citationControlling the mass action of α‐synuclein in Parkinson’s disease
Kim, C., & Lee, S. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05612.x · Cited by 105 · see citing works
Self-citationNeuronal and glial accumulation of α- and β-synucleins in human lipidoses
Suzuki, K., Iseki, E., Togo, T., Yamaguchi, A., Katsuse, O., Katsuyama, K., Kanzaki, S., Shiozaki, K., Kawanishi, C., Yamashita, S., et al. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0264-z · Cited by 83 · see citing works
Transmissible spongiform encephalopathies, amyloidoses and yeast prions: Common threads?
Caughey, B. W. (2000) · Nature Medicine · doi:10.1038/77476 · Cited by 71 · see citing works
Neuronal accumulation of α- and β-synucleins in the brain of a GM2 gangliosidosis mouse model
Suzuki, K., Iseki, E., Katsuse, O., Yamaguchi, A., Katsuyama, K., Aoki, I., Yamanaka, S., & Kosaka, K. (2003) · Neuroreport · doi:10.1097/00001756-200303240-00004 · Cited by 55 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [33]Lee H-J, et al. Neuron-to-glia transmission of α-synuclein causes glial inclusion formation and immune responses in synucleinopathies. J Exp Med. 2009 in press. [Google Scholar]
Cited by
Sorted by citations
Non-motor features of Parkinson disease
Schapira, A. H. V., Chaudhuri, K. R., & Jenner, P. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.62 · Cited by 2,053 · see citing works
Self-propagation of pathogenic protein aggregates in neurodegenerative diseases
Jucker, M., & Walker, L. C. (2013) · Nature · doi:10.1038/nature12481 · Cited by 1,663 · see citing works
-Synuclein in Parkinson's Disease
Stefanis, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009399 · Cited by 1,446 · see citing works
Colonic bacterial composition in Parkinson's disease
Keshavarzian, A., Green, S. J., Engen, P. A., Voigt, R. M., Naqib, A., Forsyth, C. B., Mutlu, E., & Shannon, K. M. (2015) · Movement Disorders · doi:10.1002/mds.26307 · Cited by 1,281 · see citing works
Goedert, M., Spillantini, M. G., Del Tredici, K., & Braak, H. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.242 · Cited by 1,190 · 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
Distinct Tau Prion Strains Propagate in Cells and Mice and Define Different Tauopathies
Sanders, D. W., Kaufman, S. K., DeVos, S. L., Sharma, A. M., Mirbaha, H., Li, A., Barker, S. J., Foley, A. C., Thorpe, J. R., Serpell, L. C., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.04.047 · Cited by 986 · see citing works
Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats
Holmqvist, S., Chutna, O., Bousset, L., Aldrin-Kirk, P., Li, W., Björklund, T., Wang, Z.-Y., Roybon, L., Melki, R., & Li, J.-Y. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1343-6 · Cited by 925 · 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
Lee, H.-J., Suk, J.-E., Patrick, C., Bae, E.-J., Cho, J.-H., Rho, S., Hwang, D., Masliah, E., & Lee, S.-J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.081125 · Cited by 877 · see citing works
Self-citationBendor, J. T., Logan, T. P., & Edwards, R. H. (2013) · Neuron · doi:10.1016/j.neuron.2013.09.004 · Cited by 825 · see citing works
A new pathway for mitochondrial quality control: Mitochondrial-derived vesicles
Sugiura, A., McLelland, G., Fon, E. A., & McBride, H. M. (2014) · The EMBO Journal · doi:10.15252/embj.201488104 · Cited by 862 · see citing works
Obeso, J. A., Stamelou, M., Goetz, C. G., Poewe, W., Lang, A. E., Weintraub, D., Burn, D., Halliday, G. M., Bezard, E., Przedborski, S., et al. (2017) · Movement Disorders · doi:10.1002/mds.27115 · Cited by 859 · see citing works
Kim, C., Ho, D.-H., Suk, J.-E., You, S., Michael, S., Kang, J., Joong Lee, S., Masliah, E., Hwang, D., Lee, H.-J., et al. (2013) · Nature Communications · doi:10.1038/ncomms2534 · Cited by 856 · see citing works
Self-citationHansen, C., Angot, E., Bergström, A.-L., Steiner, J. A., Pieri, L., Paul, G., Outeiro, T. F., Melki, R., Kallunki, P., Fog, K., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci43366 · Cited by 842 · see citing works
Prion-like mechanisms in neurodegenerative diseases
Frost, B., & Diamond, M. I. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2786 · Cited by 776 · 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
Spreading of pathology in neurodegenerative diseases: a focus on human studies
Brettschneider, J., Tredici, K. D., Lee, V. M.-Y., & Trojanowski, J. Q. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3887 · Cited by 790 · see citing works
Human iPSC-based modeling of late-onset disease via progerin-induced aging
Miller, J. D., Ganat, Y. M., Kishinevsky, S., Bowman, R. L., Liu, B., Tu, E. Y., Mandal, P. K., Vera, E., Shim, J.-W., Kriks, S., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.11.006 · Cited by 777 · see citing works
Cell-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
Schulz-Schaeffer, W. J. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0711-0 · Cited by 627 · see citing works
Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders
Jucker, M., & Walker, L. C. (2011) · Annals of Neurology · doi:10.1002/ana.22615 · Cited by 622 · see citing works
Trans-cellular Propagation of Tau Aggregation by Fibrillar Species
Kfoury, N., Holmes, B. B., Jiang, H., Holtzman, D. M., & Diamond, M. I. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.346072 · Cited by 552 · see citing works
Microglial exosomes facilitate α-synuclein transmission in Parkinson’s disease
Guo, M., Wang, J., Zhao, Y., Feng, Y., Han, S., Dong, Q., Cui, M., & Tieu, K. (2020) · Brain · doi:10.1093/brain/awaa090 · Cited by 522 · see citing works
Pan-Montojo, F., Anichtchik, O., Dening, Y., Knels, L., Pursche, S., Jung, R., Jackson, S., Gille, G., Spillantini, M. G., Reichmann, H., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008762 · Cited by 524 · see citing works
Chen, S. G., Stribinskis, V., Rane, M. J., Demuth, D. R., Gozal, E., Roberts, A. M., Jagadapillai, R., Liu, R., Choe, K., Shivakumar, B., et al. (2016) · Scientific Reports · doi:10.1038/srep34477 · Cited by 463 · see citing works
Self-citationVagotomy and Parkinson disease: A Swedish register–based matched-cohort study
Liu, B., Fang, F., Pedersen, N. L., Tillander, A., Ludvigsson, J. F., Ekbom, A., Svenningsson, P., Chen, H., & Wirdefeldt, K. (2017) · Neurology · doi:10.1212/wnl.0000000000003961 · Cited by 447 · see citing works
Extracellular vesicles in neurodegenerative disease — pathogenesis to biomarkers
Thompson, A. G., Gray, E., Heman-Ackah, S. M., Mäger, I., Talbot, K., Andaloussi, S. E., Wood, M. J., & Turner, M. R. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2016.68 · Cited by 431 · 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
Pan-Montojo, F., Schwarz, M., Winkler, C., Arnhold, M., O'Sullivan, G. A., Pal, A., Said, J., Marsico, G., Verbavatz, J.-M., Rodrigo-Angulo, M., et al. (2012) · Scientific Reports · doi:10.1038/srep00898 · Cited by 405 · see citing works
Exploring Braak’s hypothesis of Parkinson’s disease
Rietdijk, C. D., Perez-Pardo, P., Garssen, J., van Wezel, R. J. A., & Kraneveld, A. D. (2017) · Frontiers in Neurology · doi:10.3389/fneur.2017.00037 · Cited by 395 · see citing works
Gao, H.-M., Zhang, F., Zhou, H., Kam, W., Wilson, B., & Hong, J.-S. (2011) · Environmental Health Perspectives · doi:10.1289/ehp.1003013 · Cited by 355 · see citing works
“The occurrence of α-syn–positive inclusions in neurons grafted into the brains of PD patients and a transgenic (Tg) PD model (Desplats et al. 2009; Kordower et al. 2008; Li et al. 2008; Mendez et al. 2008) further emphasizes a pivotal role of α-syn in ongoing disease progression and host-to-graft disease propagation.”
BackgroundScheiblich, H., Dansokho, C., Mercan, D., Schmidt, S. V., Bousset, L., Wischhof, L., Eikens, F., Odainic, A., Spitzer, J., Griep, A., et al. (2021) · Cell · doi:10.1016/j.cell.2021.09.007 · Cited by 360 · see citing works
Mechanisms of Molecular Mimicry Involving the Microbiota in Neurodegeneration
Friedland, R. P. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-142841 · Cited by 338 · see citing works
Human Astrocytes Transfer Aggregated Alpha-Synuclein via Tunneling Nanotubes
Rostami, J., Holmqvist, S., Lindström, V., Sigvardson, J., Westermark, G. T., Ingelsson, M., Bergström, J., Roybon, L., & Erlandsson, A. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.0983-17.2017 · Cited by 339 · 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
Vagal neurocircuitry and its influence on gastric motility
Travagli, R. A., & Anselmi, L. (2016) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.76 · Cited by 323 · see citing works
Daniele, S. G., Béraud, D., Davenport, C., Cheng, K., Yin, H., & Maguire-Zeiss, K. A. (2015) · Science Signaling · doi:10.1126/scisignal.2005965 · Cited by 303 · see citing works
Freeman, D., Cedillos, R., Choyke, S., Lukic, Z., McGuire, K., Marvin, S., Burrage, A. M., Sudholt, S., Rana, A., O'Connor, C., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062143 · Cited by 289 · see citing works
The prion hypothesis in Parkinson's disease: braak to the future
Visanji, N. P., Brooks, P. L., Hazrati, L.-N., & Lang, A. E. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-2 · Cited by 278 · see citing works
Toll-Like Receptor 4 Promotes α-Synuclein Clearance and Survival of Nigral Dopaminergic Neurons
Stefanova, N., Fellner, L., Reindl, M., Masliah, E., Poewe, W., & Wenning, G. K. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.04.013 · Cited by 272 · see citing works
Self-citationAlpha-synuclein cell-to-cell transfer and seeding in grafted dopaminergic neurons in vivo
Angot, E., Steiner, J. A., Lema Tomé, C. M., Ekström, P., Mattsson, B., Björklund, A., & Brundin, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039465 · Cited by 270 · see citing works
Kaufman, S. K., Del Tredici, K., Thomas, T. L., Braak, H., & Diamond, M. I. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1855-6 · Cited by 259 · see citing works
Spreading of Neurodegenerative Pathology via Neuron-to-Neuron Transmission of -Amyloid
Nath, S., Agholme, L., Kurudenkandy, F. R., Granseth, B., Marcusson, J., & Hallbeck, M. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0615-12.2012 · Cited by 244 · see citing works
Pathogenesis of synaptic degeneration in Alzheimer's disease and Lewy body disease
Overk, C. R., & Masliah, E. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.01.015 · Cited by 242 · see citing works
Self-citationα-Synuclein in gut endocrine cells and its implications for Parkinson’s disease
Chandra, R., Hiniker, A., Kuo, Y.-M., Nussbaum, R. L., & Liddle, R. A. (2017) · JCI Insight · doi:10.1172/jci.insight.92295 · Cited by 236 · see citing works
Microglia affect α-synuclein cell-to-cell transfer in a mouse model of Parkinson’s disease
George, S., Rey, N. L., Tyson, T., Esquibel, C., Meyerdirk, L., Schulz, E., Pierce, S., Burmeister, A. R., Madaj, Z., Steiner, J. A., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0335-3 · Cited by 229 · see citing works
Tau Internalization is Regulated by 6-O Sulfation on Heparan Sulfate Proteoglycans (HSPGs)
Rauch, J. N., Chen, J. J., Sorum, A. W., Miller, G. M., Sharf, T., See, S. K., Hsieh-Wilson, L. C., Kampmann, M., & Kosik, K. S. (2018) · Scientific Reports · doi:10.1038/s41598-018-24904-z · Cited by 211 · see citing works
Therapeutic targeting of autophagy in neurodegenerative and infectious diseases
Rubinsztein, D. C., Bento, C. F., & Deretic, V. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20150956 · Cited by 202 · see citing works
Prion-like Properties of Tau Protein: The Importance of Extracellular Tau as a Therapeutic Target
Holmes, B. B., & Diamond, M. I. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.r114.549295 · Cited by 202 · see citing works
The Gut-Brain Axis in Parkinson’s Disease: Possibilities for Food-Based Therapies
Perez-Pardo, P., Kliest, T., Dodiya, H. B., Broersen, L. M., Garssen, J., Keshavarzian, A., & Kraneveld, A. D. (2017) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2017.05.042 · Cited by 203 · see citing works
Ngolab, J., Trinh, I., Rockenstein, E., Mante, M., Florio, J., Trejo, M., Masliah, D., Adame, A., Masliah, E., & Rissman, R. A. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0445-5 · Cited by 200 · see citing works
Self-citationRetractedMutant huntingtin is present in neuronal grafts in huntington disease patients
Cicchetti, F., Lacroix, S., Cisbani, G., Vallières, N., Saint‐Pierre, M., St‐Amour, I., Tolouei, R., Skepper, J. N., Hauser, R. A., Mantovani, D., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24174 · Cited by 193 · see citing works
Molecular and Biological Compatibility with Host Alpha-Synuclein Influences Fibril Pathogenicity
Luk, K. C., Covell, D. J., Kehm, V. M., Zhang, B., Song, I. Y., Byrne, M. D., Pitkin, R. M., Decker, S. C., Trojanowski, J. Q., & Lee, V. M.-Y. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.08.053 · Cited by 191 · see citing works
Prion-like spread of protein aggregates in neurodegeneration
Polymenidou, M., & Cleveland, D. W. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20120741 · Cited by 184 · see citing works
Neuropathology of multiple system atrophy: New thoughts about pathogenesis
Jellinger, K. A. (2014) · Movement Disorders · doi:10.1002/mds.26052 · Cited by 181 · see citing works
Prion-like transmission of neuronal huntingtin aggregates to phagocytic glia in the Drosophila brain
Pearce, M. M. P., Spartz, E. J., Hong, W., Luo, L., & Kopito, R. R. (2015) · Nature Communications · doi:10.1038/ncomms7768 · Cited by 159 · see citing works
Peterson, C. T. (2020) · Journal of Evidence-Based Integrative Medicine · doi:10.1177/2515690x20957225 · Cited by 160 · see citing works
Schildknecht, S., Gerding, H. R., Karreman, C., Drescher, M., Lashuel, H. A., Outeiro, T. F., Di Monte, D. A., & Leist, M. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12226 · Cited by 148 · see citing works
RETRACTED ARTICLE: LRRK2 kinase regulates α-synuclein propagation via RAB35 phosphorylation
Bae, E.-J., Kim, D.-K., Kim, C., Mante, M., Adame, A., Rockenstein, E., Ulusoy, A., Klinkenberg, M., Jeong, G. R., Bae, J. R., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05958-z · Cited by 149 · see citing works
Self-citationRetractedDiet in Parkinson’s Disease: Critical Role for the Microbiome
Jackson, A., Forsyth, C. B., Shaikh, M., Voigt, R. M., Engen, P. A., Ramirez, V., & Keshavarzian, A. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.01245 · Cited by 145 · see citing works
Wennström, M., Surova, Y., Hall, S., Nilsson, C., Minthon, L., Boström, F., Hansson, O., & Nielsen, H. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053250 · Cited by 141 · see citing works
Mechanisms of protein toxicity in neurodegenerative diseases
Chung, C. G., Lee, H., & Lee, S. B. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2854-4 · Cited by 142 · see citing works
Self-citationIntercellular Spread of Protein Aggregates in Neurodegenerative Disease
Davis, A. A., Leyns, C. E. G., & Holtzman, D. M. (2018) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100617-062636 · Cited by 131 · see citing works
Iba, M., Kim, C., Sallin, M., Kwon, S., Verma, A., Overk, C., Rissman, R. A., Sen, R., Sen, J. M., & Masliah, E. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01888-0 · Cited by 120 · see citing works
Self-citationRetractedDilsizoglu Senol, A., Samarani, M., Syan, S., Guardia, C. M., Nonaka, T., Liv, N., Latour-Lambert, P., Hasegawa, M., Klumperman, J., Bonifacino, J. S., et al. (2021) · PLOS Biology · doi:10.1371/journal.pbio.3001287 · Cited by 134 · see citing works
Alpha-Synuclein: Mechanisms of Release and Pathology Progression in Synucleinopathies
Brás, I. C., & Outeiro, T. F. (2021) · Cells · doi:10.3390/cells10020375 · Cited by 136 · see citing works
The complex relationships between microglia, alpha-synuclein, and LRRK2 in Parkinson's disease
Schapansky, J., Nardozzi, J. D., & LaVoie, M. J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2014.09.049 · Cited by 132 · see citing works
Pathogenic 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 · see citing works
Imaging transcriptomics of brain disorders
Arnatkeviciute, A., Fulcher, B. D., Bellgrove, M. A., & Fornito, A. (2022) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2021.10.002 · Cited by 113 · see citing works
Neuroinvasion of α-Synuclein Prionoids after Intraperitoneal and Intraglossal Inoculation
Breid, S., Bernis, M. E., Babila, J. T., Garza, M. C., Wille, H., & Tamgüney, G. (2016) · Journal of Virology · doi:10.1128/jvi.01399-16 · Cited by 103 · see citing works
Gut bacterial composition in a mouse model of Parkinson’s disease
Perez-Pardo, P., Dodiya, H. B., Engen, P. A., Naqib, A., Forsyth, C. B., Green, S. J., Garssen, J., Keshavarzian, A., & Kraneveld, A. D. (2018) · Beneficial Microbes · doi:10.3920/bm2017.0202 · 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
Non-cell-autonomous Neurotoxicity of α-synuclein Through Microglial Toll-like Receptor 2
Kim, C., Lee, H.-J., Masliah, E., & Lee, S.-J. (2016) · Experimental Neurobiology · doi:10.5607/en.2016.25.3.113 · Cited by 92 · see citing works
Self-citationThe toxicity of tau in Alzheimer disease: turnover, targets and potential therapeutics
Pritchard, S. M., Dolan, P. J., Vitkus, A., & Johnson, G. V. W. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01273.x · Cited by 89 · see citing works
Kumaran, R., & Cookson, M. R. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv236 · Cited by 86 · see citing works
Oligodendroglial α‐synucleinopathy‐driven neuroinflammation in multiple system atrophy
Hoffmann, A., Ettle, B., Battis, K., Reiprich, S., Schlachetzki, J. C. M., Masliah, E., Wegner, M., Kuhlmann, T., Riemenschneider, M. J., & Winkler, J. (2019) · Brain Pathology · doi:10.1111/bpa.12678 · Cited by 83 · see citing works
Self-citationDoxycycline Inhibits α-Synuclein-Associated Pathologies in Vitro and in Vivo
Dominguez-Meijide, A., Parrales, V., Vasili, E., González-Lizárraga, F., König, A., Lázaro, D. F., Lannuzel, A., Haik, S., Del Bel, E., Chehín, R., et al. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105256 · Cited by 81 · see citing works
LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies
Kim, C., Beilina, A., Smith, N., Li, Y., Kim, M., Kumaran, R., Kaganovich, A., Mamais, A., Adame, A., Iba, M., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aay0399 · Cited by 79 · see citing works
Self-citationInhibition of synucleinopathic seeding by rationally designed inhibitors
Sangwan, S., Sahay, S., Murray, K. A., Morgan, S., Guenther, E. L., Jiang, L., Williams, C. K., Vinters, H. V., Goedert, M., & Eisenberg, D. S. (2020) · eLife · doi:10.7554/elife.46775 · Cited by 79 · see citing works
Rapid macropinocytic transfer of α-synuclein to lysosomes
Bayati, A., Banks, E., Han, C., Luo, W., Reintsch, W. E., Zorca, C. E., Shlaifer, I., Del Cid Pellitero, E., Vanderperre, B., McBride, H. M., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111102 · Cited by 57 · see citing works
Primary cilia and autophagic dysfunction in Huntington’s disease
Kaliszewski, M., Knott, A. B., & Bossy-Wetzel, E. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2015.80 · Cited by 55 · see citing works
Valera, E., Spencer, B., Mott, J., Trejo, M., Adame, A., Mante, M., Rockenstein, E., Troncoso, J. C., Beach, T. G., Masliah, E., et al. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00329 · Cited by 55 · see citing works
Self-citationPukaß, K., Goldbaum, O., & Richter‐Landsberg, C. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13256 · Cited by 49 · see citing works
Post-COVID-19 Parkinsonism and Parkinson’s Disease Pathogenesis: The Exosomal Cargo Hypothesis
Mysiris, D. S., Vavougios, G. D., Karamichali, E., Papoutsopoulou, S., Stavrou, V. T., Papayianni, E., Boutlas, S., Mavridis, T., Foka, P., Zarogiannis, S. G., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179739 · Cited by 25 · see citing works
Drobny, A., Ngo, P. A., Neurath, M. F., Zunke, F., & López-Posadas, R. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.655123 · Cited by 24 · see citing works
Membrane interaction to intercellular spread of pathology in Alzheimer’s disease
Valappil, D. K., Mini, N. J., Dilna, A., & Nath, S. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.936897 · Cited by 19 · see citing works
Animal modeling an oligodendrogliopathy – multiple system atrophy
Bleasel, J. M., Halliday, G. M., & Kim, W. S. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0279-6 · Cited by 19 · see citing works
- Authors
- Desplats, P., Lee, H.-J., Bae, E.-J., Patrick, C., Rockenstein, E., Crews, L., Spencer, B., Masliah, E., & Lee, S.-J.
- Affiliations
- University of California San Diego (US)
- Konkuk University (KR)
- Seoul National University (KR)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-08-04
- Volume
- 106
- Issue
- 31
- Pages
- 13010-13015
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2722313
- OpenAlex
- W1977267085
- Cited by
- 1,485
- References
- 32
- Citations by year
- 2026: 30 · 2025: 50 · 2024: 60 · 2023: 49 · 2022: 82 · 2021: 96 · 2020: 92 · 2019: 106 · 2018: 98 · 2017: 107 · 2016: 109 · 2015: 106 · 2014: 108 · 2013: 113 · 2012: 106
- FWCI
- 59.11
- Type
- journal article
- Language
- en
- Update notices
- correction (2009-10-13)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Korea Science and Engineering Foundation
- Ministry of Education, Science and Technology
- National Institutes of Health (AG5131, AG‐18440, AG10435)
- National Institute on Aging (P01AG010435, R37AG018440, R01AG018440, P50AG005131, AG-5131, AG 18440, AG02074, AG10435)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- alpha-synuclein, Parkinson's disease, Lewy bodies, cell-to-cell transmission, neuronal precursors, endocytosis, protein aggregation, lysosomal dysfunction, protein quality control, apoptosis, caspase-3, neurodegeneration, proteinopathies, transgenic mouse model
- MeSH terms
- Animals, Biological Transport, Cell Line, Humans, Mice, Inbred C57BL, Mice, Transgenic, Synaptic Transmission, Neurons, Lewy Bodies, Apoptosis, Stem Cell Transplantation, Mice, Rats, alpha-Synuclein
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 ›
Are you an author, or do you see a problem with this page? Request a review