Restoring Bcl-xL levels benefits a mouse model of spinal muscular atrophy

被引：36

作者：

Tsai, Li-Kai ^{[2
,3
]}

Tsai, Ming-Shiun ^{[4
]}

Ting, Chen-Hung

Wang, Sue-Hong ^{[5
]}

Li, Hung ^{[1
,6
]}

机构：

[1] Acad Sinica, Inst Mol Biol, Taipei 11529, Taiwan

[2] Natl Taiwan Univ Hosp, Dept Neurol, Taipei 100, Taiwan

[3] Natl Taiwan Univ, Coll Med, Taipei 100, Taiwan

[4] Da Yeh Univ, Dept Bioind, Da Tsuen, Chang Hua, Taiwan

[5] Chung Shan Med Univ, Dept Biomed Sci, Taichung, Taiwan

[6] China Med Univ & Hosp, Dept Neurol, Ctr Neuropsychiat, Taichung 404, Taiwan

来源：

NEUROBIOLOGY OF DISEASE | 2008年 / 31卷 / 03期

关键词：

apoptosis; Bcl-xL; motor neuron disease; spinal muscular atrophy;

D O I：

10.1016/j.nbd.2008.05.014

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Currently, no curative treatment is available for spinal muscular atrophy (SMA). Since the degeneration of spinal motor neurons in SMA is mediated by apoptosis, over-expression of an anti-apoptotic factor, Bcl-x(L), may benefit SMA. Here, we crossed a mouse model of SMA with Bcl-x(L) transgenic mice to create SMA/Bcl-x(L) mice. The Bcl-x(L) expression in the spinal neurons of SMA/Bcl-xL mice was nearly double that in SMA mice. SMA/Bcl-xL mice showed preserved motor function, normalized electrophysiological tests, diminished muscle atrophy, and less motor neuron degeneration. In addition, the life span of SMA/Bcl-x(L) mice was 1.5 times longer than that of SMA mice. Therefore, over-expression of Bcl-xL has a potential for amelioration of SMA, and Bcl-x(L), may be another attractive therapeutic target other than survival motor neuron (SMN) protein for use in future drug screening for SMA. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：361 / 367

页数：7

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