Redox dysregulation as a driver for DNA damage and its relationship to neurodegenerative diseases  

作　　者：Sina Shadfar Sonam Parakh Md Shafi Jamali Julie D.Atkin 

机构地区：[1]Centre for Motor Neuron Disease Research,Macquarie Medical School,Macquarie University,Sydney,NSW 2109,Australia [2]La Trobe Institute for Molecular Science,La Trobe University,Bundoora,Melbourne,VIC 3086,Australia

出　　处：《Translational Neurodegeneration》2023年第1期604-637,共34页转化神经变性病（英文）

基　　金：supported by an Australian National Health and Medical Research Council(NHMRC)Dementia Teams Research Grant(1095215);Macquarie University MQCRF fellowship,Fight MND Foundation,and Motor Neuron Disease Research Australia.

摘　　要：Redox homeostasis refers to the balance between the production of reactive oxygen species(ROS)as well as reactive nitrogen species(RNS),and their elimination by antioxidants.It is linked to all important cellular activities and oxidative stress is a result of imbalance between pro-oxidants and antioxidant species.Oxidative stress perturbs many cellular activities,including processes that maintain the integrity of DNA.Nucleic acids are highly reactive and therefore particularly susceptible to damage.The DNA damage response detects and repairs these DNA lesions.Efficient DNA repair processes are therefore essential for maintaining cellular viability,but they decline considerably during aging.DNA damage and deficiencies in DNA repair are increasingly described in age-related neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis and Huntington’s disease.Furthermore,oxidative stress has long been associated with these conditions.Moreover,both redox dysregulation and DNA damage increase significantly during aging,which is the biggest risk factor for neurodegenerative diseases.However,the links between redox dysfunction and DNA damage,and their joint contributions to pathophysiology in these conditions,are only just emerging.This review will discuss these associations and address the increasing evidence for redox dysregulation as an important and major source of DNA damage in neurodegenerative disorders.Understanding these connections may facilitate a better understanding of disease mechanisms,and ultimately lead to the design of better therapeutic strategies based on preventing both redox dysregulation and DNA damage.

关 键 词：Redox dysregulation DNA damage NEURODEGENERATION Reactive oxygen species Oxidative stress 

分 类 号：R741[医药卫生—神经病学与精神病学]