The α-ketoglutarate dehydrogenase complex in neurodegeneration

被引：164

作者：

Gibson, GE ^{[1
]}

Park, LCH ^{[1
]}

Sheu, KFR ^{[1
]}

Blass, JP ^{[1
]}

Calingasan, NY ^{[1
]}

机构：

[1] Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, Burke Med Res Inst, White Plains, NY 10605 USA

来源：

NEUROCHEMISTRY INTERNATIONAL | 2000年 / 36卷 / 02期

关键词：

D O I：

10.1016/S0197-0186(99)00114-X

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Altered energy metabolism is characteristic of many neurodegenerative disorders. Reductions in the key mitochondrial enzyme complex, the alpha-ketoglutarate dehydrogenase complex (KGDHC), occur in a number of neurodegenerative disorders including Alzheimer's Disease (AD). The reductions in KGDHC activity may be responsible for the decreases in brain metabolism, which occur in these disorders. KGDHC can be inactivated by several mechanisms, including the actions of free radicals (Reactive Oxygen Species, ROS). Other studies have associated specific forms of one of the genes encoding KGDHC (namely the DLST gene) with AD, Parkinson's disease, as well as other neurodegenerative diseases. Reductions in KGDHC activity can be plausibly linked to several aspects of brain dysfunction and neuropathology in a number of neurodegenerative diseases. Further studies are needed to assess mechanisms underlying the sensitivity of KGDHC to oxidative stress and the relation of KGDHC deficiency to selective vulnerability in neurodegenerative diseases. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：97 / 112

页数：16

共 111 条

[1] ISOLATION, CHARACTERIZATION, AND MAPPING OF GENE ENCODING DIHYDROLIPOYL SUCCINYLTRANSFERASE (E2K) OF HUMAN ALPHA-KETOGLUTARATE DEHYDROGENASE COMPLEX [J].