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Cited by 641

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Subcellular Localization of Wild-Type and Parkinson's Disease-Associated Mutant α-Synuclein in Human and Transgenic Mouse Brain

Open access
Kahle, Philipp J., Neumann, Manuela, Ozmen, Laurence, Müller, Veronika, Jacobsen, Helmut, Schindzielorz, Alice, Okochi, Masayasu, Leimer, Uwe, van der Putten, Herman, Probst, Alphonse, Kremmer, Elisabeth, Kretzschmar, Hans A., Haass, Christian·2000·The Journal of Neuroscience

Abstract

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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Crossref · 10.1523/jneurosci.20-17-06365.2000

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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
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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CoChat. (2026). Citation check: Subcellular Localization of Wild-Type and Parkinson's Disease-Associated Mutant α-Synuclein in Human and Transgenic Mouse Brain. https://app.cochat.ai/papers/10.1523/jneurosci.20-17-06365.2000
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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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