Mitochondria and reactive oxygen and nitrogen species in neurological disorders and stroke: Therapeutic implications

被引:95
作者
Bolanos, Juan P. [1 ]
Moro, Maria A. [2 ]
Lizasoain, Ignacio [2 ]
Almeida, Angeles [1 ,3 ]
机构
[1] Univ Salamanca, Dept Biochem & Mol Biol, Inst Neurociencias Castilla & Leon, Salamanca 37007, Spain
[2] Univ Complutense Madrid, Fac Med, Dept Farmacol, E-28040 Madrid, Spain
[3] Hosp Univ Salamanca, Inst Estudios Ciencias Salud Castilla & Leon, Salamanca 37007, Spain
关键词
Mitochondria; Oxidative stress; Nitric oxide; Neurodegeneration; Stroke; Therapeutics; Pharmacology; NITRIC-OXIDE SYNTHASE; CYTOCHROME-C-OXIDASE; FOCAL CEREBRAL-ISCHEMIA; KETOGLUTARATE DEHYDROGENASE COMPLEX; AMYLOID PRECURSOR PROTEIN; TRANSGENIC MOUSE MODELS; FREE-RADICAL GENERATION; CENTRAL-NERVOUS-SYSTEM; BCL-2 FAMILY PROTEINS; CYCLIC-GMP FORMATION;
D O I
10.1016/j.addr.2009.05.009
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Mitochondria represent both the main source and target of reactive oxygen and nitrogen species (RONS). In view of the large energy expenditure made by neurons during neurotransmission, an intact mitochondrial function is of paramount importance for the correct function of the brain. Accordingly, the search of therapeutic strategies against situations in which there is an abnormal brain function, such as neurological disorders and stroke, should be focused towards mitochondria. Here, we have reviewed the normal and abnormal mitochondrial bioenergetics and dynamics, highlighting the relevance that, for these processes in the brain RONS exert. Evidence suggests that disruption of mitochondrial bioenergetics and dynamics may have a critical role in the pathogenesis of these brain diseases. Drug therapies directed toward providing safer mitochondria are currently under both pre- and clinical investigations. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:1299 / 1315
页数:17
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