神经退行性疾病中的线粒体功能障碍与炎性小体激活：机制及治疗意义

Mitochondrial dysfunction and inflammasome activation in neurodegenerative diseases: Mechanisms and therapeutic implications.

作者信息

Hamzeh Olia, Rabiei Fatemeh, Shakeri Mahdi, Parsian Hadi, Saadat Payam, Rostami-Mansoor Sahar

机构信息

Student Research Committee, Babol University of Medical Sciences, Babol, Iran; Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; Department of Clinical Biochemistry, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.

Student Research Committee, Babol University of Medical Sciences, Babol, Iran.

出版信息

Mitochondrion. 2023 Oct 28. doi: 10.1016/j.mito.2023.10.003.

DOI:10.1016/j.mito.2023.10.003

PMID:39492438

Abstract

Impaired mitochondrial function is crucial to the pathogenesis of several neurodegenerative diseases. It causes the release of mitochondrial DNA (mtDNA), mitochondrial reactive oxygen species (mtROS), ATP, and cardiolipin, which activate the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome. NLRP3 inflammasome is an important innate immune system element contributing to neuroinflammation and neurodegeneration. Therefore, targeting the NLRP3 inflammasome has become an interesting therapeutic approach for treating neurodegenerative diseases. This review describes the role of mitochondrial abnormalities and over-activated inflammasomes in the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), and Friedrich ataxia (FRDA). We also discuss the therapeutic strategies focusing on signaling pathways associated with inflammasome activation, which potentially alleviate neurodegenerative symptoms and impede disease progression.

摘要

线粒体功能受损在几种神经退行性疾病的发病机制中至关重要。它会导致线粒体DNA（mtDNA）、线粒体活性氧（mtROS）、ATP和心磷脂的释放，这些物质会激活核苷酸结合寡聚化结构域（NOD）样受体蛋白3（NLRP3）炎性小体。NLRP3炎性小体是先天性免疫系统的一个重要组成部分，会导致神经炎症和神经退行性变。因此，靶向NLRP3炎性小体已成为治疗神经退行性疾病的一种有吸引力的治疗方法。这篇综述描述了线粒体异常和过度激活的炎性小体在神经退行性疾病如阿尔茨海默病（AD）、帕金森病（PD）、亨廷顿病（HD）、多发性硬化症（MS）、肌萎缩侧索硬化症（ALS）和弗里德里希共济失调（FRDA）进展中的作用。我们还讨论了针对与炎性小体激活相关信号通路的治疗策略，这些策略可能减轻神经退行性症状并阻碍疾病进展。