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Oxidative Nerve Cell Death in AlzheimersDisease and Stroke: Antioxidants asNeuroprotective Compounds

Identifieur interne : 001864 ( Main/Exploration ); précédent : 001863; suivant : 001865

Oxidative Nerve Cell Death in AlzheimersDisease and Stroke: Antioxidants asNeuroprotective Compounds

Auteurs : C. Behl ; B. Moosmann

Source :

RBID : ISTEX:82ECE8E5750417CCF1C4FE5AF889A622ED522D6D

Abstract

Many neurodegenerative disorders and syndromes are associated with an excessive generation of reactive oxygen species (ROS) and oxidative stress. The pathways to nerve cell death induced by diverse potential neurotoxins such as peptides, excitatory amino acids, cytokines or synthetic drugs commonly share oxidative downstream processes, which can cause either an acute oxidative destruction or activate secondary events leading to apoptosis. The pathophysiological role of ROS has been intensively studied in in vitro and in vivo models of chronic neurodegenerative diseases such as Alzheimers disease (AD) and of syndromes associated with rapid nerve cell loss as occuring in stroke. In AD, oxidative neuronal cell dysfunction and cell death caused by protofibrils and aggregates of the ADassociated amyloid β protein (Aβ) may causally contribute to pathogenesis and progression. ROS and reactive nitrogen species also take part in the complex cascade of events and the detrimental effects occuring during ischemia and reperfusion in stroke. Direct antioxidants such as chainbreaking free radical scavengers can prevent oxidative nerve cell death. Although there is ample experimental evidence demonstrating neuroprotective activities of direct antioxidants in vitro, the clinical evidence for antioxidant compounds to act as protective drugs is relatively scarce. Here, the neuroprotective potential of antioxidant phenolic structures including αtocopherol (vitamin E) and 17βestradiol (estrogen) in vitro is summarized. In addition, the antioxidant and cytoprotective activities of lipophilic tyrosine and tryptophancontaining structures are discussed. Finally, an outlook is given on the neuroprotective potential of aromatic amines and imines, which may comprise novel lead structures for antioxidant drug design.

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DOI: 10.1515/BC.2002.053


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