Oxidative stress induces amyloid-like aggregate formation of NACP/α-synuclein in vitro

被引：383

作者：

Hashimoto, M

Hsu, LJ

Xia, Y

Takeda, A

Sisk, A

Sundsmo, M

Masliah, E ^{[1
]}

机构：

[1] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA

来源：

NEUROREPORT | 1999年 / 10卷 / 04期

关键词：

Alzheimer's disease; amyloid; NACP alpha-synuclein; neurodegeneration; oxidative stress; Parkinson's disease;

D O I：

10.1097/00001756-199903170-00011

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

THE precursor of non-amyloid beta protein component of Alzheimer's disease amyloid (NACP/alpha-synuclein), found in Lewy bodies of Parkinson's disease (PD), is a presynaptic protein genetically linked to some familial types PD Mechanisms of abnormal NACP/alpha-synuclein aggregation in neurodegenerative diseases are unclear. Since oxidative stress might play a role in PD pathogenesis, we investigated the role of iron and peroxide in NACP/alpha-synuclein aggregation. Immunoblot analysis showed that human NACP/alpha-synuclein (but not beta-synuclein) aggregated in the presence of ferric ion and was inhibited by the iron chelator deferoxamine. Ferrous ion was not effective by itself, but it potentially aggregated NACP/alpha-synuclein in the presence of hydrogen peroxide. NACP/alpha-synuclein aggregates displayed strong thioflavine-S and congo-red reactivity, reminiscent of amyloid. This study suggests that NACP/alpha-synuclein aggregation might be closely related to oxidative reactions which may play a critical role in neurodegeneration in disorders with Lewy bodies. NeuroReport 10:717-721 (C) 1999 Lippincott Williams & Wilkins.

引用

页码：717 / 721

页数：5

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