Free radical damage and oxidative stress in Huntington's disease.
Bioenergetic defects and oxidative stress may be critical links in an excitotoxic mechanism of neuronal death. Oxidative stress, a condition describing the production of oxygen radicals beyond a threshold for proper antioxidant neutralization, has been implicated as a pathologic condition in several neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. In addition, oxygen radicals are known to be important mediators in acute pathologies, in the theory of senescence, cancer, as well as our healthy immune system. Although free radicals may have a special chemical nature which allows them to perform important cellular functions, they are a damaging entity whose reactivity may play a part in the development of cellular compromises that can kill a neuron. In this review, the free radicals in biological systems, the defense systems against them, and the damaging interactions, i.e., oxidative stress, which they confer are discussed. The descriptions provided raise the hypothesis that an imbalance between the production and removal of radicals would be abrasive on a neuron. Accordingly, the neurodegeneration initially caused by gene mutation in Huntington's disease may be further worsened by free radical damage underlied by oxidative stress. This article reviews existing data on the free radical damage and the oxidative stress, which are primarily directed towards Parkinson's disease and Alzheimer's disease, and whenever possible relates such mechanisms to Huntington's disease.
Borlongan
C V
CV
Department of Surgery, University of South Florida College of Medicine, Tampa, USA.
Kanning
K
K
Poulos
S G
SG
Freeman
T B
TB
Cahill
D W
DW
Sanberg
P R
PR
D000544:Alzheimer Disease / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism; D004734:Energy Metabolism; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000975:Antioxidants; D005609:Free Radicals; D017382:Reactive Oxygen Species