A mitochondrial etiology of Alzheimer and Parkinson disease.
A mitochondrial etiology of Alzheimer and Parkinson disease.
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DOI：
10.1016/j.bbagen.2011.08.008
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发表时间：
2012-05
影响因子：
3
通讯作者：
Wallace, Douglas C.
中科院分区：
文献类型：
--
作者：
Coskun, Pinar;Wyrembak, Joanne;Schriner, Samual E.;Chen, Hsiao-Wen;Marciniack, Christine;LaFerla, Frank;Wallace, Douglas C.
阿尔茨海默病（AD）和帕金森病（PD）的遗传学和病理生理学表现复杂。然而，线粒体功能障碍是这些和其他神经退行性疾病中常见的观察结果。我们认为，AD和PD的现有数据可以纳入基于线粒体遗传学和病理生理学的单一综合范式。罕见的AD和PD染色体病例可以解释为影响线粒体功能、质量控制和线粒体DNA（mtDNA）完整性。线粒体DNA谱系、单倍型群（如H5a单倍型群，其含有mtDNA tRNAGln A8336G变异体）是AD和PD的重要危险因素。体细胞mtDNA突变在AD、PD和唐氏综合征和痴呆（DSAD）中在大脑和全身都升高。AD、DS和DSAD大脑也存在mtDNA ND6 mRNA水平降低、mtDNA拷贝数改变和A β代谢紊乱。经典的AD遗传变化纳入3XTg-AD（APP，Tau，PS1）小鼠导致前脑尺寸减小，3XTg-AD雄性动物的线粒体呼吸终生减少，3XTg-AD雌性动物的呼吸和复合物I和IV活性最初升高，随着年龄的增长而显著下降。因此，线粒体功能障碍为AD、PD和其他神经退行性疾病提供了统一的遗传学和病理生理学解释。
The genetics and pathophysiology of Alzheimer Disease (AD) and Parkinson Disease (PD) appears complex. However, mitochondrial dysfunction is a common observation in these and other neurodegenerative diseases We argue that the available data on AD and PD can be incorporated into a single integrated paradigm based on mitochondrial genetics and pathophysiology. Rare chromosomal cases of AD and PD can be interpreted as affecting mitochondrial function, quality control, and mitochondrial DNA (mtDNA) integrity. mtDNA lineages, haplogroups, such haplogroup H5a which harbors the mtDNA tRNAGln A8336G variant, are important risk factors for AD and PD. Somatic mtDNA mutations are elevated in AD, PD, and Down Syndrome and Dementia (DSAD) both in brains and also systemically. AD, DS, and DSAD brains also have reduced mtDNA ND6 mRNA levels, altered mtDNA copy number, and perturbed Aβ metabolism. Classical AD genetic changes incorporated into the 3XTg-AD (APP, Tau, PS1) mouse result in reduced forebrain size, life-long reduced mitochondrial respiration in 3XTg-AD males, and initially elevated respiration and complex I and IV activities in 3XTg-AD females which markedly declines with age. Therefore, mitochondrial dysfunction provides a unifying genetic and pathophysiology explanation for AD, PD, and other neurodegenerative diseases.
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DOI：
10.1016/j.bbadis.2009.07.007
发表时间：
2010-01
影响因子：
6.2
作者：
Devi, Latha;Anandatheerthavarada, Hindupur K.
通讯作者：
Anandatheerthavarada, Hindupur K.
影响因子：
5.3
作者：
Crouch, PJ;Blake, R;Trounce, IA
通讯作者：
Trounce, IA
影响因子：
4.8
作者：
Chen, Hung-Kai;Ji, Zhong-Sheng;Mahley, Robert W.
通讯作者：
Mahley, Robert W.
影响因子：
5.3
作者：
Carrieri, G;Bonafè, M;De Benedictis, G
通讯作者：
De Benedictis, G
DOI：
10.1073/pnas.1006586107
发表时间：
2010-10-26
影响因子：
11.1
作者：
Du, Heng;Guo, Lan;Yan, Shirley ShiDu
通讯作者：
Yan, Shirley ShiDu