Amyloid-β:: An antioxidant that becomes a pro-oxidant and critically contributes to Alzheimer's disease

被引:140
作者
Kontush, A [1 ]
机构
[1] Univ Hamburg, Hosp Eppendorf, Med Clin, D-20246 Hamburg, Germany
关键词
amyloid-beta; Alzheimer's disease; antioxidant; transition metals; oxidation; lipoproteins; free radicals;
D O I
10.1016/S0891-5849(01)00688-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Elevated production of amyloid-beta (A beta) as a preventive antioxidant for brain lipoproteins under the action of increased oxidative stress in aging is postulated to represent a major event in the development of Alzheimer's disease (AD). Increase in A beta production is followed by chelation of transition metal ions by A beta, accumulation of A beta -metal lipoprotein aggregates, production of reactive oxygen species and neurotoxicity. Chelation of copper by A beta is proposed to be a most important part of this pathway, because A beta binds copper stronger than other transition metals and because copper is a more efficient catalyst of oxidation than other metals. This amyloid-binds-copper (ABC) model does not remove A beta peptide from its central place in our current thinking of AD, but rather places additional factors in the center of discussion. Most importantly, they embrace pathological mechanisms known to develop in aging (which is the major risk factor for AD), such as increased production of reactive oxygen species by mitochondria, that are positioned upstream relative to the generation of A beta. (C) 2001 Elsevier Science Inc.
引用
收藏
页码:1120 / 1131
页数:12
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