The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Subcellular Localization of Wild-Type and Parkinson's Disease-Associated Mutant α-Synuclein in Human and Transgenic Mouse Brain
Open accessAbstract
Mutations in the alpha-synuclein (alphaSYN) gene are associated with rare cases of familial Parkinson's disease, and alphaSYN is a major component of Lewy bodies and Lewy neurites. Here we have investigated the localization of wild-type and mutant [A30P]alphaSYN as well as betaSYN at the cellular and subcellular level. Our direct comparative study demonstrates extensive synaptic colocalization of alphaSYN and betaSYN in human and mouse brain. In a sucrose gradient equilibrium centrifugation assay, a portion of betaSYN floated into lower density fractions, which also contained the synaptic vesicle marker synaptophysin. Likewise, wild-type and [A30P]alphaSYN were found in floating fractions. Subcellular fractionation of mouse brain revealed that both alphaSYN and betaSYN were present in synaptosomes. In contrast to synaptophysin, betaSYN and alphaSYN were recovered from the soluble fraction upon lysis of the synaptosomes. Synaptic colocalization of alphaSYN and betaSYN was directly visualized by confocal microscopy of double-stained human brain sections. The Parkinson's disease-associated human mutant [A30P]alphaSYN was found to colocalize with betaSYN and synaptophysin in synapses of transgenic mouse brain. However, in addition to their normal presynaptic localization, transgenic wild-type and [A30P]alphaSYN abnormally accumulated in neuronal cell bodies and neurites throughout the brain. Thus, mutant [A30P]alphaSYN does not fail to be transported to synapses, but its transgenic overexpression apparently leads to abnormal cellular accumulations.
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Cites
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Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
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AlaSOPro mutation in the gene encoding α-synuclein in Parkinson's disease
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Mice Lacking α-Synuclein Display Functional Deficits in the Nigrostriatal Dopamine System
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“LBs were aSYN-positive in LB variant of Alzheimer’s disease, familial Alzheimer’s disease, and Down’s syndrome (Lippa et al., 1998, 1999; Takeda et al., 1998b ), as well as in neurodegeneration with brain iron accumulation type 1 (formerly known as Hallervorden‐ Spatz disease) (Arawaka et al., 1998; Wakabayashi et al.…”
BackgroundLippa, C. F., Fujiwara, H., Mann, D. M. A., Giasson, B., Baba, M., Schmidt, M. L., Nee, L. E., O'Connell, B., Pollen, D. A., St. George-Hyslop, P., et al. (1998) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65722-7 · Cited by 533
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The rat brain synucleins; family of proteins transiently associated with neuronal membrane
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Cited by
Neuronal α-Synucleinopathy with Severe Movement Disorder in Mice Expressing A53T Human α-Synuclein
Giasson, B. I., Duda, J. E., Quinn, S. M., Zhang, B., Trojanowski, J. Q., & Lee, V. M.-Y. (2002) · Neuron · doi:10.1016/s0896-6273(02)00682-7 · Cited by 1,266
Shimura, H., Schlossmacher, M. G., Hattori, N., Frosch, M. P., Trockenbacher, A., Schneider, R., Mizuno, Y., Kosik, K. S., & Selkoe, D. J. (2001) · Science · doi:10.1126/science.1060627 · Cited by 1,053
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
Bendor, J. T., Logan, T. P., & Edwards, R. H. (2013) · Neuron · doi:10.1016/j.neuron.2013.09.004 · Cited by 825
Martin, L. J., Pan, Y., Price, A. C., Sterling, W., Copeland, N. G., Jenkins, N. A., Price, D. L., & Lee, M. K. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4308-05.2006 · Cited by 684
Metadata
- Authors
- Kahle, P. J., Neumann, M., Ozmen, L., Müller, V., Jacobsen, H., Schindzielorz, A., Okochi, M., Leimer, U., van der Putten, H., Probst, A., Kremmer, E., Kretzschmar, H. A., & Haass, C.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2000-09-01
- Volume
- 20
- Issue
- 17
- Pages
- 6365-6373
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2131207606
- Cited by
- 641
- References
- 11
- FWCI
- 19.21
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Kahle, P. J., Neumann, M., Ozmen, L., Müller, V., Jacobsen, H., Schindzielorz, A., Okochi, M., Leimer, U., van der Putten, H., Probst, A., Kremmer, E., Kretzschmar, H. A., & Haass, C. (2000). Subcellular Localization of Wild-Type and Parkinson's Disease-Associated Mutant α-Synuclein in Human and Transgenic Mouse Brain. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.20-17-06365.2000
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.