Alzheimer's disease and oxidative stress: implications for novel therapeutic approaches.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a deadly outcome. AD is the leading cause of senile dementia and although the pathogenesis of this disorder is not known, various hypotheses have been developed based on experimental data accumulated since the initial description of this disease by Alois Alzheimer about 90 years ago. Most approaches to explain the pathogenesis of AD focus on its two histopathological hallmarks, the amyloid beta protein- (A(beta)-) loaded senile plaques and the neurofibrillary tangles, which consist of the filament protein tau. Various lines of genetic evidence support a central role of A(beta) in the pathogenesis of AD and an increasing number of studies show that oxidation reactions occur in AD and that A(beta) may be one molecular link between oxidative stress and AD-associated neuronal cell death. A(beta) itself can be neurotoxic and can induce oxidative stress in cultivated neurons. A(beta) is, therefore, one player in the concert of oxidative reactions that challenge neurons besides inflammatory reactions which are also associated with the AD pathology. Consequently, antioxidant approaches for the prevention and therapy of AD are of central interest. Experimental as well as clinical data show that lipophilic antioxidants, such as vitamin E and estrogens, are neuroprotective and may help patients suffering from AD. While an additional intensive elucidation of the cellular and molecular events of neuronal cell death in AD will, ultimately, lead to novel drug targets, various antioxidants are already available for a further exploitation of their preventive and therapeutic potential. reserved
Behl
C
C
Max Planck Institute of Psychiatry, Munich, Germany. chris@mpipsykl.mpg.de
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000502:physiology; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D004967:Estrogens / Q000627:therapeutic use; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use; D018384:Oxidative Stress / Q000502:physiology*
D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D004967:Estrogens; D018696:Neuroprotective Agents