The complex effects of miR-146a in the pathogenesis of Alzheimer's disease  

作　　者：Yunfan Long Jiajia Liu Yu Wang Haidong Guo Guohong Cui 

机构地区：[1]Department of Neurology,Shanghai No.9 People’s Hospital,Shanghai Jiaotong University School of Medicine,Shanghai,China [2]Academy of Integrative Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai,China [3]School of Integrative Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai,China [4]Department of Neurology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai,China

出　　处：《Neural Regeneration Research》2025年第5期1309-1323,共15页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.81970991(to GC);Program of Shanghai Academic Research Leader,No.22XD1423400(to HG)。

摘　　要：Alzheimer's disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral abnormalities.Neuroinflammatory plaques formed through the extracellular deposition of amyloid-βproteins,as well as neurofibrillary tangles formed by the intracellular deposition of hyperphosphorylated tau proteins,comprise two typical pathological features of Alzheimer's disease.Besides symptomatic treatment,there are no effective therapies for delaying Alzheimer's disease progression.MicroRNAs(miR)are small,non-coding RNAs that negatively regulate gene expression at the transcriptional and translational levels and play important roles in multiple physiological and pathological processes.Indeed,miR-146a,a NF-κB-regulated gene,has been extensively implicated in the development of Alzheimer's disease through several pathways.Research has demonstrated substantial dysregulation of miR-146a both during the initial phases and throughout the progression of this disorder.Mi R-146a is believed to reduce amyloid-βdeposition and tau protein hyperphosphorylation through the TLR/IRAK1/TRAF6 pathway;however,there is also evidence supporting that it can promote these processes through many other pathways,thus exacerbating the pathological manifestations of Alzheimer's disease.It has been widely reported that miR-146a mediates synaptic dysfunction,mitochondrial dysfunction,and neuronal death by targeting m RNAs encoding synapticrelated proteins,mitochondrial-related proteins,and membrane proteins,as well as other mRNAs.Regarding the impact on glial cells,miR-146a also exhibits differential effects.On one hand,it causes widespread and sustained inflammation through certain pathways,while on the other hand,it can reverse the polarization of astrocytes and microglia,alleviate neuroinflammation,and promote oligodendrocyte progenitor cell differentiation,thus maintaining the normal function of the myelin sheath and exerting a protective effect on neurons.In this review,we provide a comprehensive analysis of the involvement of

关 键 词：Alzheimer's disease amyloid-β glial cells MICRORNAS MIR-146A neuroinflammatory 

分 类 号：R749.16[医药卫生—神经病学与精神病学]