Microglial senescence in neurodegeneration:Insights,implications,and therapeutic opportunities  

作　　者：Tobiloba Samuel Olajide Toheeb O.Oyerinde Omolabake I.Omotosho Oritoke M.Okeowo Olayemi J.Olajide Omamuyouwi M.Ijomone 

机构地区：[1]Laboratory for Experimental and Translational Neurobiology,University of Medical Sciences,Ondo,Ondo,Nigeria [2]Department of Physiology,School of Basic Medical Science,Federal University of Technology,Akure,Ondo,Nigeria [3]Center for Studies in Behavioral Neurobiology,Department of Psychology,Concordia University,Montreal,Quebec,Canada [4]Division of Neurobiology,Department of Anatomy,Faculty of Basic Medical Sciences,University of Ilorin,Ilorin,Kwara,Nigeria [5]Department of Molecular Pharmacology,Albert Einstein College of Medicine,Bronx,New York,USA

出　　处：《Neuroprotection》2024年第3期182-195,共14页神经保护（英文）

基　　金：NIH-FIC,Grant/Award Number:K43TW011920。

摘　　要：The existing literature on neurodegenerative diseases(NDDs)reveals a common pathological feature:the accumulation of misfolded proteins.However,the heterogeneity in disease onset mechanisms and the specific brain regions affected complicates the understanding of the diverse clinical manifestations of individual NDDs.Dementia,a hallmark symptom across various NDDs,serves as a multifaceted denominator,contributing to the clinical manifestations of these disorders.There is a compelling hypothesis that therapeutic strategies capable of mitigating misfolded protein accumulation and disrupting ongoing pathogenic processes may slow or even halt disease progression.Recent research has linked disease-associated microglia to their transition into a senescent state—characterized by irreversible cell cycle arrest—in aging populations and NDDs.Although senescent microglia are consistently observed in NDDs,few studies have utilized animal models to explore their role in disease pathology.Emerging evidence from experimental rat models suggests that disease-associated microglia exhibit characteristics of senescence,indicating that deeper exploration of microglial senescence could enhance our understanding of NDD pathogenesis and reveal novel therapeutic targets.This review underscores the importance of investigating microglial senescence and its potential contributions to the pathophysiology of NDDs,including Alzheimer's disease,Parkinson's disease,Huntington's disease,and amyotrophic lateral sclerosis.Additionally,it highlights the potential of targeting microglial senescence through iron chelation and senolytic therapies as innovative approaches for treating age-related NDDs.

关 键 词：aging FERRITIN microglia neurodegenerative diseases senescence-associated secretory phenotype senescent 

分 类 号：R745[医药卫生—神经病学与精神病学]