Signaling interactions among neurons impact cell fitness and death in Alzheimer's disease

作     者：Catherine Yeates Prajakta Deshpande Madhuri Kango-Singh Amit Singh Catherine Yeates;Prajakta Deshpande;Madhuri Kango-Singh;Amit Singh

作者机构：Department of BiologyUniversity of DaytonDaytonOHUSA Premedical ProgramUniversity of DaytonDaytonOHUSA Center for Tissue Regeneration and Engineering at Dayton(TREND)University of DaytonDaytonOHUSA The Integrative Science and Engineering CenterUniversity of DaytonDaytonOHUSA Center for Genomic Advocacy(TCGA)Indiana State UniversityTerre HauteINUSA 

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

年 卷 期：2023年第18卷第4期

页      面：784-789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)] 100203[医学-老年医学] 10[医学] 

基　　金：supported by 1RO1EY032959-01,NIH1R15GM124654-01 from NIH Schuellein Chair Endowment Fund and STEM Catalyst Grant and start-up support from the University of Dayton(to AS,MKS is Co-PI on NIH RO1 and Co-I on NIH R15)。 

主　　题：Alzheimer’s disease amyloid-beta 42 mediated neurodegeneration cell competition Drosophila c-Jun N-terminal kinase signaling suboptimal cell super competition super competitor cell two clone-approach wild type cell 

摘      要：The pathology of Alzheimer’s disease involves a long preclinical period,where the characteristic clinical symptoms of the changes in the brain are undetectable.During the preclinical period,homeostatic mechanisms may help prevent widespread cell death.Evidence has pointed towards selective cell death of diseased neurons playing a potentially protective role.As the disease progresses,dysregulation of signaling pathways that govern cell death contributes to neurodegeneration.Aberrant activation of the c-Jun N-terminal kinase pathway has been established in human and animal models of Alzheimer’s disease caused by amyloid-beta 42-or tau-mediated neurodegeneration.Clonal mosaic studies in Drosophila that examine amyloid-beta 42 in a subset of neurons suggest complex interplay between amyloid-beta 42-expressing and wild-type cells.This review examines the role of c-Jun N-terminal kinase signaling in the context of cell competition and short-range signaling interactions between amyloid-beta 42-expressing and wild-type neurons.Cell competition is a conserved phenomenon regulating tissue integrity by assessing the fitness of cells relative to their neighbors and eliminating suboptimal cells.Somatic clones of amyloid-beta 42 that juxtapose genetically distinct neuronal cell populations show promise for studying neurodegeneration.Generating genetic mosaics with labeled clones of amyloid-beta 42-or tau-expressing and wild-type neurons will allow us to understand how short-range signaling alterations trigger cell death in neurons and thereby contribute to the progression of Alzheimer’s disease.These approaches have the potential to uncover biomarkers for early Alzheimer’s disease detection and new therapeutic targets for intervention.