Oxidative stress: free radical production in neural degeneration.
It is not yet established whether oxidative stress is a major cause of cell death or simply a consequence of an unknown pathogenetic factor. Concerning chronic diseases, as Parkinson's and Alzheimer's disease are assumed to be, it is possible that a gradual impairment of cellular defense mechanisms leads to cell damage because of toxic substances being increasingly formed during normal cellular metabolism. This point of view brings into consideration the possibility that, besides exogenous factors, the pathogenetic process of neurodegeration is triggered by endogenous mechanisms, either by an endogenous toxin or by inherited metabolic disorders, which become progressively more evident with aging. In the following review, we focus on the oxidative stress theory of neurodegeneration, on excitotoxin-induced cell damage and on impairment of mitochondrial function as three major noxae being the most likely causes of cell death either independently or in connection with each other. First, having discussed clinical, pathophysiological, pathological and biochemical features of movement and cognitive disorders, we discuss the common features of these biochemical theories of neurodegeneration separately. Second, we attempt to evaluate possible biochemical links between them and third, we discuss experimental findings that confirm or rule out the involvement of any of these theories in neurodegeneration. Finally, we report some therapeutic strategies evolved from each of these theories.
Götz
M E
ME
Department of Psychiatry, University of Würzburg, Germany.
Künig
G
G
Riederer
P
P
Youdim
M B
MB
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D016923:Cell Death; D003071:Cognition / Q000502:physiology; D004734:Energy Metabolism; D018846:Excitatory Amino Acids / Q000502:physiology; D005609:Free Radicals; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009069:Movement Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009410:Nerve Degeneration; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000009:adverse effects
D000975:Antioxidants; D018846:Excitatory Amino Acids; D005609:Free Radicals; D017382:Reactive Oxygen Species