Mouse model of multiple system atrophy α-synuclein expression in oligodendrocytes causes glial and neuronal degeneration

被引：238

作者：

Yazawa, I

Giasson, BI

Sasaki, R

Zhang, B

Joyce, S

Uryu, K

Trojanowski, JQ

Lee, VMY ^{[1
]}

机构：

[1] Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[2] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA

[3] Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19104 USA

来源：

NEURON | 2005年 / 45卷 / 06期

关键词：

D O I：

10.1016/j.neuron.2005.01.032

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Transgenic (Tg) mice overexpressing human wild-type alpha-synuclein in oligodendrocytes under the control of the 2,' 3'-cyclic nucleotide X-phosphodiesterase (CNP) promoter are shown here to recapitulate features of multiple system atrophy (MSA), including the accumulation of filamentous human alpha-synuclein aggregates in oligodendrocytes linked to their degeneration and autophagocytosis of myelin. Significantly, endogenous mouse (x-synuclein also accumulated in normal and degenerating axons and axon terminals in association with oligodendroglia and neuron loss and slowly progressive motor impairments. Our studies demonstrate that overexpression of alpha-synuclein in oligodendrocytes of mice results in MSA-like degeneration in the CNS and that a-synuclein inclusions in oligodendrocytes participate in the degeneration of neurons in MSA.

引用

页码：847 / 859

页数：13

共 44 条

[41] DISTRIBUTION OF TAU PROTEINS IN THE NORMAL HUMAN CENTRAL AND PERIPHERAL NERVOUS-SYSTEM [J].