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Neurosci Lett. 2011 Mar 17;491(2):148-52. doi: 10.1016/j.neulet.2011.01.026. Epub 2011 Jan 14.

Over-expression of α-synuclein 98 triggers intracellular oxidative stress and enhances susceptibility to rotenone.

Author information

1
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (Key Laboratory of Bioactive Substances and Resources Utilization, Ministry of Education), 1 Xiannongtan Street, Xuanwu District, Beijing 100050, PR China.

Abstract

The α-synuclein protein is a major component of Lewy bodies found in the brains of patients with Parkinson's disease (PD). Recently, α-synuclein 98 (α-syn98), a small isoform of the wild type protein was isolated. The neurotoxicity of this protein was assessed by over-expressing α-syn98 in dopaminergic cells. Enhanced expression of α-syn98 was insufficient to adversely affect the survival of neurons or to promote aggregation of the protein. However, when exposed to rotenone, α-syn98 over-expressing dopaminergic cells demonstrated significantly increased cytotoxicity and aggregate formation. Furthermore, we found enhanced basal ROS production and MDA levels in α-syn98 over-expressing neurons. High basal oxidative stress induced by α-syn98, combined with oxidative stress caused by rotenone treatment, promoted aggregate formation and significantly decreased cell viability. These data indicate that α-syn98 can enhance the susceptibility of dopaminergic neurons to oxidative insults by raising steady-state levels of oxidative stress.

PMID:
21238542
DOI:
10.1016/j.neulet.2011.01.026
[Indexed for MEDLINE]

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