Alzheimer's disease and oxygen radicals: new insights.
Alzheimer's disease (AD) is the most common form of neurodegenerative disease, with dementia, in the elderly. In addition to the presence of senile plaques and neurofibrillary tangles, the AD brain exhibits evidence for oxygen radical-mediated damage, a situation commonly known as oxidative stress. However, the ability to directly implicate this mechanism in AD has been a difficult task for several reasons. First, most of the analytical approaches used to investigate oxidative stress turned out to be unreliable. Second, the majority of the published studies have been performed in post-mortem tissues with advanced disease, leaving open the question as to whether oxidative stress is an early event or a common final step secondary to the degenerative process. The discovery of the isoprostanes, recent studies performed in living patients, and the development of transgenic animal models of AD-amyloidosis are three important factors that are helping us to better understand and define the role that oxygen radicals might play in AD pathogenesis. Here we review some of the most recent works that have supported the importance of oxygen radical-mediated damage in AD. The accumulated information points toward an earlier involvement than previously thought of oxidative stress in the pathogenesis of the disease, making this a potential target for therapeutic intervention, especially in subjects at high risk for developing AD.
Praticò
Domenico
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Department of Pharmacology, Center for Experimental Therapeutics School of Medicine, University of Pennsylvania, 421 Curie Blvd., BRB 2/3, Room 812, Philadelphia, PA 19104, USA. domenico@spirit.gcrc.upenn.edu
D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000682:Amyloid; D017382:Reactive Oxygen Species