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神经退行性疾病中的氧化应激与离子通道

Oxidative stress and ion channels in neurodegenerative diseases.

作者信息

Orfali Razan, Alwatban Adnan Z, Orfali Rawan S, Lau Liz, Chea Noble, Alotaibi Abdullah M, Nam Young-Woo, Zhang Miao

机构信息

Neuroscience Research Department, Research Centre, King Fahad Medical City, Riyadh, Saudi Arabia.

BrainExperiments.com, Montreal, QC, Canada.

出版信息

Front Physiol. 2024 Jan 29;15:1320086. doi: 10.3389/fphys.2024.1320086. eCollection 2024.

Abstract

Numerous neurodegenerative diseases result from altered ion channel function and mutations. The intracellular redox status can significantly alter the gating characteristics of ion channels. Abundant neurodegenerative diseases associated with oxidative stress have been documented, including Parkinson's, Alzheimer's, spinocerebellar ataxia, amyotrophic lateral sclerosis, and Huntington's disease. Reactive oxygen and nitrogen species compounds trigger posttranslational alterations that target specific sites within the subunits responsible for channel assembly. These alterations include the adjustment of cysteine residues through redox reactions induced by reactive oxygen species (ROS), nitration, and S-nitrosylation assisted by nitric oxide of tyrosine residues through peroxynitrite. Several ion channels have been directly investigated for their functional responses to oxidizing agents and oxidative stress. This review primarily explores the relationship and potential links between oxidative stress and ion channels in neurodegenerative conditions, such as cerebellar ataxias and Parkinson's disease. The potential correlation between oxidative stress and ion channels could hold promise for developing innovative therapies for common neurodegenerative diseases.

摘要

许多神经退行性疾病是由离子通道功能改变和突变引起的。细胞内氧化还原状态可显著改变离子通道的门控特性。已有大量与氧化应激相关的神经退行性疾病被记录,包括帕金森病、阿尔茨海默病、脊髓小脑共济失调、肌萎缩侧索硬化症和亨廷顿舞蹈症。活性氧和氮物种化合物引发翻译后改变,这些改变靶向负责通道组装的亚基内的特定位点。这些改变包括通过活性氧(ROS)诱导的氧化还原反应调节半胱氨酸残基,通过过氧亚硝酸盐由一氧化氮辅助对酪氨酸残基进行硝化和S-亚硝基化。已经直接研究了几种离子通道对氧化剂和氧化应激的功能反应。本综述主要探讨神经退行性疾病(如小脑共济失调和帕金森病)中氧化应激与离子通道之间的关系和潜在联系。氧化应激与离子通道之间的潜在相关性可能为开发常见神经退行性疾病的创新疗法带来希望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4bb/10859863/3fdf233e5136/fphys-15-1320086-g001.jpg

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