Neuronal guidance signaling in neurodegenerative diseases:Key regulators that function at neuron-glia and neuroimmune interfaces  

作　　者：Junichi Yuasa-Kawada Mariko Kinoshita-Kawada Masaki Hiramoto Satoru Yamagishi Takayasu Mishima Shin’ichiro Yasunaga Yoshio Tsuboi Nobutaka Hattori Jane Y.Wu 

机构地区：[1]Department of Neurology,Juntendo University Faculty of Medicine,Tokyo,Japan [2]The Scripps Research Institute,La Jolla,CA,USA [3]Department of Optical Neuroanatomy,Institute of Photonics Medicine,Hamamatsu University School of Medicine,Hamamatsu,Japan [4]Division of Neurology,Department of Internal Medicine,Sakura Medical Center,Toho University,Sakura,Japan [5]Department of Biochemistry,Fukuoka University Faculty of Medicine,Fukuoka,Japan [6]Department of Neurology,Center for Genetic Medicine,Lurie Cancer Center,Northwestern University Feinberg School of Medicine,Chicago,IL,USA

出　　处：《Neural Regeneration Research》2026年第2期612-635,共24页中国神经再生研究(英文版)

基　　金：supported by JSPS(KAKENHI:21K06205,23K06937,24K23419);AMED(to JYK,SaY,TM,SiY,YT,and NH);JYW had long been supported by the NIH.

摘　　要：The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathologica

关 键 词：amyloid-β axon guidance NEURODEGENERATION neuroimmune interactions neuroinflammation neuron-glia interactions neurovascular interactions SEMAPHORIN synaptic remodeling tau TDP-43 TREM2 Α-SYNUCLEIN 

分 类 号：R741[医药卫生—神经病学与精神病学]