Transforming growth factor-beta 2 causes an acute improvement in the motor performance of transgenic ALS mice

被引：25

作者：

Day, WA

Koishi, K

Nukuda, H

McLennan, IS

机构：

[1] Univ Otago, Sch Med Sci, Neuromuscular Res Grp, Dunedin, New Zealand

[2] Univ Otago, Dept Neurol, Dunedin, New Zealand

来源：

NEUROBIOLOGY OF DISEASE | 2005年 / 19卷 / 1-2期

关键词：

D O I：

10.1016/j.nbd.2005.01.010

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Amyotrophic lateral sclerosis (ALS) is fatal disorder, characterized by the loss of motoneurons. The therapeutic potential of transforming growth factor-beta 2 (TGF-beta 2) was examined using SOD1 mice. The SOD1 mice were treated with TGF-beta 2 by repeated intraperitoneal injections. The highest dose of TGF-beta 2 caused a rapid and marked improvement in the motor performance of the mice. This improvement lasted for between 2 and 3 weeks after which the TGF-beta 2-treated mice rapidly deteriorated. At postmortem, the motoneurons in the TGF-beta 2-treated SOD1 mice exhibited a large hypertrophy of their nucleoli, nuclei, and axons. In contrast, TGF-beta 2 did not reverse the mitochondrial pathology. This may explain why the beneficial effects of TGF-beta 2 and other growth factor on SOD1 mice are transient: TGF-beta 2 is stimulating the motoneurons metabolic rate while one of their key metabolic organelles is damaged. Consequently, TGF-beta 2 may be therapeutic for the forms ALS, with minimal mitochondrial involvement. (c) 2005 Elsevier Inc. All rights reserved.

引用

页码：323 / 330

页数：8

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[1] Increased survival and function of SOD1 mice after glial cell-derived neurotrophic factor gene therapy [J].