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Determining nuclear localization of alpha-synuclein in mouse brains.

Abstract
Alpha-synuclein (α-Syn) is a major component of Lewy bodies, abnormal protein aggregates that are present in neurons of patients with Parkinson's disease and other neurological disorders. Despite intensive investigation, the in vivo role of α-Syn in physiological and pathological processes is not fully understood. This study addresses a current debate on the nuclear localization of α-Syn protein in the brain. To assess the specificity of various α-Syn antibodies, we compared their staining patterns in wild-type mouse brains with that of the α-Syn knock-out mice. Among five different α-Syn antibodies tested here, two generated intensive nuclear staining throughout the normal mouse brain. However, nuclear staining by these two antibodies was also present in neurons of the α-Syn knock-out mice. This provides evidence that the nuclear signal is not specifically related to the presence of α-Syn, but it rather results from the cross-reactivity of the two antibodies to some unknown antigens in neuronal nuclei. In mouse brain neurons, endogenous α-Syn proteins are primarily localized to neuronal processes and nerve terminals but present only at low levels in the cell bodies. This is different from a generally uniform distribution of exogenously expressed α-Syn in both cytoplasm and nuclei of heterologous cells and suggests that the neuritic enrichment of α-Syn in neurons may be mediated by their specific interactions with certain structural or molecular components in the neuropil.
AuthorsZ Huang, Z Xu, Y Wu, Y Zhou
JournalNeuroscience (Neuroscience) Vol. 199 Pg. 318-32 (Dec 29 2011) ISSN: 1873-7544 [Electronic] United States
PMID22033456 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
Chemical References
  • Antibodies
  • alpha-Synuclein
Topics
  • Animals
  • Antibodies
  • Antibody Specificity
  • Blotting, Western
  • Brain (metabolism)
  • Cell Nucleus (metabolism)
  • Cross Reactions
  • Fluorescent Antibody Technique
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons (metabolism)
  • alpha-Synuclein (metabolism)

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