在胶质瘤细胞系中，脑源性神经营养因子（BDNF）由野生型α-突触核蛋白诱导产生，而非由两种突变体A30P或A53T诱导产生。

BDNF is induced by wild-type alpha-synuclein but not by the two mutants, A30P or A53T, in glioma cell line.

作者信息

Kohno Ryuichi, Sawada Hideyuki, Kawamoto Yasuhiro, Uemura Kengo, Shibasaki Hiroshi, Shimohama Shun

机构信息

Department of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyoku, Kyoto 606-8507, Japan.

出版信息

Biochem Biophys Res Commun. 2004 May 21;318(1):113-8. doi: 10.1016/j.bbrc.2004.04.012.

DOI:10.1016/j.bbrc.2004.04.012

PMID:15110760

Abstract

Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases but its etiology is unclear. Alpha-synuclein (alpha-SN) is a major component of Lewy bodies and Lewy neurites, and its missense mutations, A30P and A53T, cause familial PD. In PD, alpha-SN-positive glial inclusions are distributed mainly in the dorso-medial region of the substantia nigra, which contains most of the surviving dopaminergic neurons, suggesting that alpha-SN expression might have a neuroprotective function in glial cells. To investigate this hypothesis, we established alpha-SN transfected C6 glioma cell line clones and evaluated the expression of neurotrophins using semi-quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Brain-derived neurotrophic factor (BDNF) was induced by overexpression of wild-type alpha-SN but not by that of A30P and A53T. These data suggest that the pathogenic alpha-SN mutations, A30P or A53T, are linked to the loss of BDNF production in glial cells.

摘要

帕金森病（PD）是最常见的神经退行性疾病之一，但其病因尚不清楚。α-突触核蛋白（α-SN）是路易小体和路易神经突的主要成分，其错义突变A30P和A53T可导致家族性帕金森病。在帕金森病中，α-SN阳性胶质包涵体主要分布在黑质背内侧区域，该区域包含大多数存活的多巴胺能神经元，这表明α-SN表达可能在胶质细胞中具有神经保护功能。为了验证这一假设，我们建立了转染α-SN的C6胶质瘤细胞系克隆，并使用半定量逆转录聚合酶链反应和酶联免疫吸附测定法评估神经营养因子的表达。野生型α-SN的过表达可诱导脑源性神经营养因子（BDNF）的产生，而A30P和A53T的过表达则不能。这些数据表明，致病性α-SN突变A30P或A53T与胶质细胞中BDNF产生的丧失有关。