Bcl-2家族对神经元发育和神经退行性变的调控。

Bcl-2 family regulation of neuronal development and neurodegeneration.

作者信息

Akhtar Rizwan S, Ness Jayne M, Roth Kevin A

机构信息

Division of Pediatric Neurology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

出版信息

Biochim Biophys Acta. 2004 Mar 1;1644(2-3):189-203. doi: 10.1016/j.bbamcr.2003.10.013.

DOI:10.1016/j.bbamcr.2003.10.013

PMID:14996503

Abstract

Neuronal cell death is a key feature of both normal nervous system development and neuropathological conditions. The Bcl-2 family, via its regulation of both caspase-dependent and caspase-independent cell death pathways, is uniquely positioned to critically control neuronal cell survival. Targeted gene disruptions of specific bcl-2 family members and the generation of transgenic mice overexpressing anti- or pro-apoptotic Bcl-2 family members have confirmed the importance of the Bcl-2 family in the nervous system. Data from studies of human brain tissue and experimental animal models of neuropathological conditions support the hypothesis that the Bcl-2 family regulates cell death in the mature nervous system and suggest that pharmacological manipulation of Bcl-2 family action could prove beneficial in the treatment of human neurological conditions such as stroke and neurodegenerative diseases.

摘要

神经元细胞死亡是正常神经系统发育和神经病理状况的关键特征。Bcl-2家族通过对依赖半胱天冬酶和不依赖半胱天冬酶的细胞死亡途径的调控，在严格控制神经元细胞存活方面具有独特地位。对特定bcl-2家族成员的靶向基因破坏以及过表达抗凋亡或促凋亡Bcl-2家族成员的转基因小鼠的产生，证实了Bcl-2家族在神经系统中的重要性。来自人类脑组织研究和神经病理状况实验动物模型的数据支持这样的假说，即Bcl-2家族调节成熟神经系统中的细胞死亡，并表明对Bcl-2家族作用进行药理学操纵可能被证明对治疗人类神经系统疾病如中风和神经退行性疾病有益。