DETERMINING NUCLEAR LOCALIZATION OF ALPHA-SYNUCLEIN IN MOUSE BRAINS

Alpha-synuclein (alpha-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 alpha-Syn in physiological and pathological processes is not fully understood. This study addresses a current debate on the nuclear localization of alpha-Syn protein in the brain. To assess the specificity of various alpha-Syn antibodies, we compared their staining patterns in wild-type mouse brains with that of the alpha-Syn knock-out mice. Among five different alpha-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 alpha-Syn knock-out mice. This provides evidence that the nuclear signal is not specifically related to the presence of alpha-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 alpha-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 alpha-Syn in both cytoplasm and nuclei of heterologous cells and suggests that the neuritic enrichment of alpha-Syn in neurons may be mediated by their specific interactions with certain structural or molecular components in the neuropil. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.