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与帕金森病相关的线粒体 DNA 损伤。

Damage in Mitochondrial DNA Associated with Parkinson's Disease.

机构信息

Department of Biology and Université de Moncton, Moncton, Canada.

Canada Research Chair in Mitochondrial Signaling and Physiopathology, Université de Moncton, Moncton, Canada.

出版信息

DNA Cell Biol. 2020 Aug;39(8):1421-1430. doi: 10.1089/dna.2020.5398. Epub 2020 May 12.

Abstract

Mitochondria are the only organelles that contain their own genetic material (mtDNA). Mitochondria are involved in several key physiological functions, including ATP production, Ca homeostasis, and metabolism of neurotransmitters. Since these organelles perform crucial processes to maintain neuronal homeostasis, mitochondrial dysfunctions can lead to various neurodegenerative diseases. Several mitochondrial proteins involved in ATP production are encoded by mtDNA. Thus, any mtDNA alteration can ultimately lead to mitochondrial dysfunction and cell death. Accumulation of mutations, deletions, and rearrangements in mtDNA has been observed in animal models and patients suffering from Parkinson's disease (PD). Also, specific inherited variations associated with mtDNA genetic groups (known as mtDNA haplogroups) are associated with lower or higher risk of developing PD. Consequently, mtDNA alterations should now be considered important hallmarks of this neurodegenerative disease. This review provides an update about the role of mtDNA alterations in the physiopathology of PD.

摘要

线粒体是唯一含有自身遗传物质(mtDNA)的细胞器。线粒体参与了几种关键的生理功能,包括 ATP 生成、Ca2+ 稳态和神经递质代谢。由于这些细胞器执行维持神经元内稳态的关键过程,线粒体功能障碍可导致各种神经退行性疾病。参与 ATP 生成的几种线粒体蛋白由 mtDNA 编码。因此,mtDNA 的任何改变最终都可能导致线粒体功能障碍和细胞死亡。在帕金森病(PD)患者和动物模型中已经观察到 mtDNA 中突变、缺失和重排的积累。此外,与 mtDNA 遗传群(称为 mtDNA 单倍群)相关的特定遗传性变异与较低或较高的 PD 发病风险相关。因此,mtDNA 改变现在应该被认为是这种神经退行性疾病的重要标志。本综述提供了 mtDNA 改变在 PD 病理生理学中的作用的最新信息。

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