Neuroprotective strategies involving ROS in Alzheimer disease

被引:304
作者
Dumont, Magali [1 ]
Beal, M. Flint [1 ]
机构
[1] Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY 10065 USA
基金
美国国家卫生研究院;
关键词
Alzheimer disease; Oxidative stress; Reactive oxygen species; Therapeutic strategies; Neuroprotection; Pathology; Cognitive deficit; Free radicals; ACETYL-L-CARNITINE; TRANSGENIC MOUSE MODEL; MILD COGNITIVE IMPAIRMENT; NITRIC-OXIDE SYNTHASE; ALPHA-LIPOIC ACID; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MITOCHONDRIAL OXIDATIVE STRESS; BETA-AMYLOID PEPTIDE; TARGETING A-BETA; DOUBLE-BLIND;
D O I
10.1016/j.freeradbiomed.2010.11.026
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
Alzheimer disease (AD) is a neurodegenerative disorder in which oxidative stress is a key hallmark. It occurs early in disease pathogenesis and can exacerbate its progression. Several causes of oxidative stress have been determined over the years. First, mitochondria play an important role in the generation and accumulation of free radicals. In addition to mitochondria, inflammation can also induce oxidative damage, especially via microglia, and microglia are also important for A beta clearance. In AD, both mitochondrial function and inflammatory response are affected, leading to increased ROS formation and oxidative damage to lipid, proteins, and nucleic acids. Some other sources have also been identified. From these findings, various neuroprotective strategies against ROS-mediated damages have been elaborated in AD research. This review recapitulates some of the major strategies used to prevent oxidative stress and disease progression. Outcomes from in vitro and in vivo studies using models of AD are encouraging. However, only a few clinical trials have provided positive results in terms of slowing down cognitive decline. Nonetheless, there is still hope for improved compounds that would better target pathways implicated in ROS production. In fact, facilitating the endogenous antioxidant system by modulating transcription has great promise for AD therapy. Published by Elsevier Inc.
引用
收藏
页码:1014 / 1026
页数:13
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