Dopaminergic loss and inclusion body formation in α-synuclein mice:: Implications for neurodegenerative disorders

被引：1497

作者：

Masliah, E ^{[1
]}

Rockenstein, E

Veinbergs, I

Mallory, M

Hashimoto, M

Takeda, A

Sagara, Y

Sisk, A

Mucke, L

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

[3] Yokohama City Univ, Sch Med, Dept Psychiat, Yokohama, Kanagawa 236, Japan

[4] Univ Calif San Francisco, Gladstone Inst Neurol Dis, San Francisco, CA 94141 USA

[5] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94141 USA

来源：

SCIENCE | 2000年 / 287卷 / 5456期

关键词：

D O I：

10.1126/science.287.5456.1265

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

To elucidate the role of the synaptic protein alpha-synuclein in neurodegenerative disorders, transgenic mice expressing wild-type human alpha-synuclein were generated. Neuronal expression of human alpha-synuclein resulted in progressive accumulation of alpha-synuclein-and ubiquitin-immunoreactive inclusions in neurons in the neocortex, hippocampus, and substantia nigra. Ultrastructural analysis revealed both electron-dense intranuclear deposits and cytoplasmic inclusions. These alterations were associated with Loss of dopaminergic terminals in the basal ganglia and with motor impairments. These results suggest that accumulation of wild-type alpha-synuclein may play a causal role in Parkinson's disease and related conditions.

引用

页码：1265 / 1269

页数：5

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