脑铁沉积与衰老的自由基-线粒体理论

Brain iron deposition and the free radical-mitochondrial theory of ageing.

作者信息

Schipper Hyman M

机构信息

Centre for Neurotranslational Research and Bloomfield Centre for Research in Ageing, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, Que., Canada. hyman@

出版信息

Ageing Res Rev. 2004 Jul;3(3):265-301. doi: 10.1016/j.arr.2004.02.001.

DOI:10.1016/j.arr.2004.02.001

PMID:15231237

Abstract

The central hypothesis of this paper states that oxidative stress, augmented iron deposition, and mitochondrial insufficiency in the ageing and degenerating CNS constitute a single neuropathological 'lesion', and that the advent of one component of this triad obligates the appearance of the others. Evidence in support of this unifying perspective is adduced from human neuropathological studies, experimental paradigms of ageing-associated neurological disorders, and a comprehensive model of astroglial senescence. A pivotal role for the enzyme, heme oxygenase-1 (HO-1) in consolidating this tripartite lesion in the ageing and diseased CNS is emphasized. The data are discussed in the context of a revised 'free radical-mitochondrial-metal' theory of brain ageing, and some scientific and clinical implications of the latter are considered.

摘要

本文的核心假说是，在衰老和退化的中枢神经系统中，氧化应激、铁沉积增加以及线粒体功能不全构成了单一的神经病理学“病变”，并且这三者中任何一个因素的出现都会促使其他因素的出现。支持这一统一观点的证据来自人类神经病理学研究、衰老相关神经疾病的实验范式以及星形胶质细胞衰老的综合模型。本文强调了血红素加氧酶-1（HO-1）在衰老和患病中枢神经系统中巩固这一三联病变过程中的关键作用。我们在修订后的大脑衰老“自由基-线粒体-金属”理论背景下对这些数据进行了讨论，并考虑了该理论的一些科学和临床意义。