Shifting equilibriums in Alzheimer’s disease: the complex roles of microglia in neuroinflammation, neuronal survival and neurogenesis

作     者：Sophie C. Gray Kerri J. Kinghorn Nathaniel S. Woodling Sophie C. Gray;Kerri J. Kinghorn;Nathaniel S. Woodling

作者机构：Institute of Healthy Ageing and Department of Genetics Evolution and Environment University College London 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2020年第15卷第7期

页      面：1208-1219页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：the Academy of Medical Sciences the Rosetrees Trust (KJK) the Alzheimer’s Society (NSW) for their kind support 

主　　题：adult neurogenesis Alzheimer's disease IGF-1 microglia neuroinflammation Trem2 

摘      要：Alzheimer s disease is the leading cause of *** increased prevalence in developed countries,due to the sharp rise in ageing populations,presents one of the costliest challenges to modern *** order to find disease-modifying therapies to confront this challenge,a more complete understanding of the pathogenesis of Alzheimer s disease is *** studies have revealed increasing evidence for the roles played by microglia,the resident innate immune system cells of the *** the well-established roles of microglia in reacting to pathogens and inflammatory stimuli,there is now a growing literature describing both protective and detrimental effects for individual cytokines and chemokines produced by microglia in Alzheimer s disease.A smaller but increasing number of studies have also addressed the divergent roles played by microglial neurotrophic and neurogenic factors,and how their perturbation may play a key role in the pathogenesis of Alzheimer s *** we review recent findings on the roles played by microglia in neuroinflammation,neuronal survival and neurogenesis in Alzheimer s *** each case,landmark studies have provided evidence for the divergent ways in which microglia can either promote neuronal function and survival,or perturb neuronal function,leading to cell *** many cases,the secreted molecules of microglia can lead to divergent effects depending on the magnitude and context of microglial *** suggests that microglial functions must be maintained in a fine equilibrium,in order to support healthy neuronal function,and that the cellular microenvironment in the Alzheimer s disease brain disrupts this fine balance,leading to ***,an understanding of microglial homeostasis,both in health and across the trajectory of the disease state,will improve our understanding of the pathogenic mechanisms underlying Alzheimer s disease,and will hopefully lead to the development of microglial-base