线粒体 DNA 紊乱在阿尔茨海默病和帕金森病发病机制中的作用。

Role of mtDNA disturbances in the pathogenesis of Alzheimer's and Parkinson's disease.

机构信息

Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Kateřinská 32, 121 08 Prague 2, Czech Republic.

Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Kateřinská 32, 121 08 Prague 2, Czech Republic; Department of Analytical Chemistry, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague 6, Dejvice, Czech Republic.

出版信息

DNA Repair (Amst). 2020 Jul-Aug;91-92:102871. doi: 10.1016/j.dnarep.2020.102871. Epub 2020 May 21.

DOI:10.1016/j.dnarep.2020.102871

PMID:32502755

Abstract

Neurodegenerative diseases (e.g. Alzheimer's and Parkinson's disease) are becoming increasingly problematic to healthcare systems. Therefore, their underlying mechanisms are trending topics of study in medicinal research. Numerous studies have evidenced a strong association between mitochondrial DNA disturbances (e.g. oxidative damage, mutations, and methylation shifts) and the initiation and progression of neurodegenerative diseases. Therefore, this review discusses the risk and development of neurodegenerative diseases in terms of disturbances in mitochondrial DNA and as a part of a complex ecosystem that includes other important mechanisms (e.g. neuroinflammation and the misfolding and aggregation of amyloid-β peptides, α-synuclein, and tau proteins). In addition, the influence of individual mitochondrial DNA haplogroups on the risk and development of neurodegenerative diseases is also described and discussed.

摘要

神经退行性疾病（如阿尔茨海默病和帕金森病）对医疗系统的影响越来越大。因此，它们的潜在机制是医学研究的热门课题。许多研究表明，线粒体 DNA 紊乱（如氧化损伤、突变和甲基化转移）与神经退行性疾病的发生和发展之间存在很强的关联。因此，本综述讨论了线粒体 DNA 紊乱与神经退行性疾病的风险和发展之间的关系，并将其作为包括其他重要机制（如神经炎症以及淀粉样β肽、α-突触核蛋白和 tau 蛋白的错误折叠和聚集）在内的复杂生态系统的一部分进行了讨论。此外，还描述和讨论了个体线粒体 DNA 单倍群对神经退行性疾病风险和发展的影响。