The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
A Pathologic Cascade Leading to Synaptic Dysfunction in -Synuclein-Induced Neurodegeneration
Open accessAbstract
Several neurodegenerative diseases are typified by intraneuronal alpha-synuclein deposits, synaptic dysfunction, and dementia. While even modest alpha-synuclein elevations can be pathologic, the precise cascade of events induced by excessive alpha-synuclein and eventually culminating in synaptotoxicity is unclear. To elucidate this, we developed a quantitative model system to evaluate evolving alpha-synuclein-induced pathologic events with high spatial and temporal resolution, using cultured neurons from brains of transgenic mice overexpressing fluorescent-human-alpha-synuclein. Transgenic alpha-synuclein was pathologically altered over time and overexpressing neurons showed striking neurotransmitter release deficits and enlarged synaptic vesicles; a phenotype reminiscent of previous animal models lacking critical presynaptic proteins. Indeed, several endogenous presynaptic proteins involved in exocytosis and endocytosis were undetectable in a subset of transgenic boutons ("vacant synapses") with diminished levels in the remainder, suggesting that such diminutions were triggering the overall synaptic pathology. Similar synaptic protein alterations were also retrospectively seen in human pathologic brains, highlighting potential relevance to human disease. Collectively the data suggest a previously unknown cascade of events where pathologic alpha-synuclein leads to a loss of a number of critical presynaptic proteins, thereby inducing functional synaptic deficits.
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Cites
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
Kramer, M. L., & Schulz-Schaeffer, W. J. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4564-06.2007 · Cited by 571
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
Self-citationDouble-knockout mice for α- and β-synucleins: Effect on synaptic functions
Chandra, S., Fornai, F., Kwon, H.-B., Yazdani, U., Atasoy, D., Liu, X., Hammer, R. E., Battaglia, G., German, D. C., Castillo, P. E., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406283101 · Cited by 438
β-Amyloid Monomers Are Neuroprotective
Giuffrida, M. L., Caraci, F., Pignataro, B., Cataldo, S., De Bona, P., Bruno, V., Molinaro, G., Pappalardo, G., Messina, A., Palmigiano, A., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.1736-09.2009 · Cited by 421
Hyperphosphorylation and insolubility of α‐synuclein in transgenic mouse oligodendrocytes
Kahle, P. J., Neumann, M., Ozmen, L., Müller, V., Jacobsen, H., Spooren, W., Fuss, B., Mallon, B., Macklin, W. B., Fujiwara, H., et al. (2002) · The EMBO Reports · doi:10.1093/embo-reports/kvf109 · Cited by 314
Synaptic vesicle protein 2 enhances release probability at quiescent synapses
Custer, K. L., Austin, N. S., Sullivan, J. M., & Bajjalieh, S. M. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2699-05.2006 · Cited by 211
Cited by
Neuropathological alterations in Alzheimer disease
Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006189 · Cited by 3,345
Self-citationBalestrino, R., & Schapira, A. H. V. (2020) · European Journal of Neurology · doi:10.1111/ene.14108 · Cited by 1,508
-Synuclein in Parkinson's Disease
Stefanis, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009399 · Cited by 1,446
Bendor, J. T., Logan, T. P., & Edwards, R. H. (2013) · Neuron · doi:10.1016/j.neuron.2013.09.004 · Cited by 825
α-synuclein in the pathophysiology of Alzheimer’s disease
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Metadata
- Authors
- Scott, D. A., Tabarean, I., Tang, Y., Cartier, A., Masliah, E., & Roy, S.
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-06-16
- Volume
- 30
- Issue
- 24
- Pages
- 8083-8095
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2017040646
- Cited by
- 353
- References
- 7
- FWCI
- 13.72
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Scott, D. A., Tabarean, I., Tang, Y., Cartier, A., Masliah, E., & Roy, S. (2010). A Pathologic Cascade Leading to Synaptic Dysfunction in -Synuclein-Induced Neurodegeneration. Journal of Neuroscience. https://doi.org/10.1523/jneurosci.1091-10.2010
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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