Antioxidants as treatment for neurodegenerative disorders

被引:180
作者
Moosmann, B
Behl, C [1 ]
机构
[1] Johannes Gutenberg Univ Mainz, Dept Pathogbiochem, D-55099 Mainz, Germany
[2] Burnham Inst, Ctr Neurosci & Aging, La Jolla, CA 92037 USA
关键词
Alzheimer's disease; amyotrophic lateral sclerosis; antioxidant; clinical trial; drug design; free radical; Huntington's disease; metabolic stabiliser; neuroprotection; oxidative stress; Parkinson's disease; vitamin;
D O I
10.1517/13543784.11.10.1407
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Oxidative stress is a ubiquitously observed hallmark of neurodegenerative disorders. Neuronal cell dysfunction and cell death due to oxidative stress may causally contribute to the pathogenesis of progressive neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, as well as acute syndromes of neurodegeneration, such as ischaemic and haemorrhagic stroke. Neuroprotective antioxidants are considered a promising approach to slowing the progression and limiting the extent of neuronal cell loss in these disorders. The clinical evidence demonstrating that antioxidant compounds can act as protective drugs in neurodegenerative disease, however, is still relatively scarce. In the following review, the available data from clinical, animal and cell biological studies regarding the role of antioxidant neuroprotection in progressive neurodegenerative disease will be summarised, focussing particularly on Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. The general complications in developing potent neuroprotective antioxidant drugs directed against these long-term degenerative conditions will also be discussed. The major challenges for drug development are the slow kinetics of disease progression, the unsolved mechanistic questions concerning the final causalities of cell death, the necessity to attain an effective permeation of the blood-brain barrier and the need to reduce the high concentrations currently required to evoke protective effects in cellular and animal model systems. Finally, an outlook as to which direction antioxidant drug development and clinical practice may be leading to in the near future will be provided.
引用
收藏
页码:1407 / 1435
页数:29
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