c-Abl kinase at the crossroads of healthy synaptic remodeling and synaptic dysfunction in neurodegenerative diseases  

作　　者：Daniela A.Gutiérrez América Chandía-Cristi María JoséYáñez Silvana Zanlungo Alejandra R.Alvarez 

机构地区：[1]Cell Signaling Laboratory,Department of Cellular and Molecular Biology,Center for Aging and Regeneration(CARE),Millennium Institute on Immunology and Immunotherapy,Biological Sciences Faculty,Pontificia Universidad Católica de Chile,Santiago,Chile [2]School of Medical Technology,Health Sciences Faculty,Universidad San Sebastian,Sede Los Leones,Santiago,Chile [3]Department of Gastroenterology,Faculty of Medicine,Pontificia Universidad Católica de Chile,Santiago,Chile

出　　处：《Neural Regeneration Research》2023年第2期237-243,共7页中国神经再生研究（英文版）

基　　金：supported by Comisión Nacional de Investigación Cientifica y Tecnologica-Chile Fondecyt 12011668(to ARA);Fondecyt 1190334(to SZ);Fondecyt 11200592(to MJY);Fondef ID21/10347(to ARA andSZ);Fondef D10E1077(to ARA and SZ);CARE-UCAFB 170005(to ARA);MSCA-RISE-2016-Lysomod-734825 European Union's Horizon 2020;Research and Innovation Program under the Marie Sklodowska-Curie grant agreement N°953489(to SZ);Millennium Science Initiative Program-ICN09_016/ICN 2021_045(to ARA)。

摘　　要：Our ability to learn and remember depends on the active formation,remodeling,and elimination of synapses.Thus,the development and growth of synapses as well as their weakening and elimination are essential for neuronal rewiring.The structural reorganization of synaptic complexes,changes in actin cytos keleton and organelle dynamics,as well as modulation of gene expression,determine synaptic plasticity.It has been proposed that dys regulation of these key synaptic homeostatic processes underlies the synaptic dysfunction observed in many neurodegenerative diseases.Much is known about downstream signaling of activated N-methyl-D-aspartate andα-amino-3-hydroxy-5-methyl-4-isoazolepro pionate receptors;howeve r,other signaling pathways can also contribute to synaptic plasticity and long-lasting changes in learning and memory.The non-receptor tyrosine kinase c-Abl(ABL1)is a key signal transducer of intra and extracellular signals,and it shuttles between the cyto plasm and the nucleus.This review focuses on c-Abl and its synaptic and neuronal functions.Here,we discuss the evidence showing that the activation of c-Abl can be detrimental to neurons,promoting the development of neurodegenerative diseases.Nevertheless,c-Abl activity seems to be in a pivotal balance between healthy synaptic plasticity,regulating dendritic spines remodeling and gene expression after cognitive training,and synaptic dysfunction and loss in neurodegenerative diseases.Thus,c-Abl genetic ablation not only improves learning and memory and modulates the brain genetic program of trained mice,but its absence provides dendritic spines resiliency against damage.Therefo re,the present review has been designed to elu cidate the common links between c-Abl regulation of structural changes that involve the actin cytos keleton and organelles dynamics,and the transc riptional program activated during synaptic plasticity.By summarizing the recent discove ries on c-Abl functions,we aim to provide an overview of how its inhibition co uld be a potentially fruitful

关 键 词：actin cytoskeleton activity-dependent plasticity Alzheimer's disease C-ABL dendritic spines learning SYNAPSE synaptic plasticity transcription tyrosine kinase 

分 类 号：R749.16[医药卫生—神经病学与精神病学]