NADH的治疗潜力:线粒体功能障碍为特征的神经退行性疾病
Therapeutic potential of NADH:in neurodegenerative diseases characterizde by mitochondrial dysfunction
陈姿伊 1王洪阳 1王秋菊1
作者信息
- 1. 解放军总医院第六医学中心耳鼻咽喉头颈外科医学部耳鼻咽喉内科耳鼻咽喉研究所国家耳鼻咽喉疾病临床医学研究中心(北京,100048)
- 折叠
摘要
还原型烟酰胺腺嘌呤二核苷酸(nicotinamide adenine dinucleotide,NADH)是能量稳态所必需的氧化还原反应的关键辅酶,参与呼吸链电子传递.NADH和其氧化对应物NAD+被称为氧化还原对,可相互转化,控制多种生物过程,如钙稳态、突触可塑性、抗凋亡和基因表达.NAD+/NADH水平降低与线粒体功能障碍密切相关,而线粒体功能障碍在众多神经退行性病变的级联反应中发挥重要作用,如帕金森病和阿尔茨海默等神经退行性疾病.听神经病(auditory neuropathy,AN)作为神经退行性疾病的一种临床生物学标记,在OPA1、AIFM1等基因突变为病因的患者中也发现3线粒体功能障碍,但目前尚无有效的治疗方法.越来越多证据表明,内源性给予NAD+或其前体,可通过改善DNA修复损伤、线粒体功能来预防和延缓疾病进展.因此,本综述聚焦于NAD+/NADH的产生代谢途径、生物学功能,探讨了 NADH对AN的治疗潜力以及可能的作用机制.
Abstract
Nicotinamide adenine dinucleotide(NADH)in its reduced form of is a key coenzyme in redox reac-tions,essential for maintaining energy homeostasis.NADH and its oxidized counterpart,NAD+,form a redox couple that regulates various biological processes,including calcium homeostasis,synaptic plasticity,anti-apopto-sis,and gene expression.The reduction of NAD+/NADH levels is closely linked to mitochondrial dysfunction,which plays a pivotal role in the cascade of various neurodegenerative disorders,including Parkinson's disease and Alzheimer's disease.Auditory neuropathy(AN)is recognized as a clinical biomarker in neurodegenerative disor-ders.Furthermore,mitochondrial dysfunction has been identified in patients with mutations in genes like OPA1 and AIFM1.However,effective treatments for these conditions are still lacking.Increasing evidence sug-gests that administratering NAD+or its precursors endogenously may potentially prevent and slow disease pro-gression by enhancing DNA repair and improving mitochondrial function.Therefore,this review concentrates on the metabolic pathways of NAD+/NADH production and their biological functions,and delves into the therapeu-tic potential and mechanisms of NADH in treating AN.
关键词
烟酰胺腺嘌呤二核苷酸/神经退行性疾病/线粒体功能障碍Key words
nicotinamide adenine dinucleotide/neurodegenerative diseases/mitochondrial dysfunction引用本文复制引用
基金项目
国家自然科学基金优秀青年基金(82222016)
国家自然科学基金重点项目(81830028)
解放军总医院优青培育专项(2020-YQPY-004)
出版年
2024
NETL
NSTL
万方数据