气候变化领域集成服务门户(CCPortal): Developmental synaptic regulator, TWEAK/Fn14 signaling, is a determinant of synaptic function in models of stroke and neurodegeneration

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DOI	10.1073/pnas.2001679118
	Developmental synaptic regulator, TWEAK/Fn14 signaling, is a determinant of synaptic function in models of stroke and neurodegeneration
	Nagy D.; Ennis K.A.; Wei R.; Su S.C.; Hinckley C.A.; Gu R.-F.; Gao B.; Massol R.H.; Ehrenfels C.; Jandreski L.; Thomas A.M.; Nelson A.; Gyoneva S.; Hajós M.; Burkly L.C.
发表日期	2021
ISSN	00278424
卷号	118 期号:6
英文摘要	Identifying molecular mediators of neural circuit development and/or function that contribute to circuit dysfunction when aberrantly reengaged in neurological disorders is of high importance. The role of the TWEAK/Fn14 pathway, which was recently reported to be a microglial/neuronal axis mediating synaptic refinement in experience-dependent visual development, has not been explored in synaptic function within the mature central nervous system. By combining electrophysiological and phosphoproteomic approaches, we show that TWEAK acutely dampens basal synaptic transmission and plasticity through neuronal Fn14 and impacts the phosphorylation state of pre- and postsynaptic proteins in adult mouse hippocampal slices. Importantly, this is relevant in two models featuring synaptic deficits. Blocking TWEAK/Fn14 signaling augments synaptic function in hippocampal slices from amyloid-beta-overexpressing mice. After stroke, genetic or pharmacological inhibition of TWEAK/ Fn14 signaling augments basal synaptic transmission and normalizes plasticity. Our data support a glial/neuronal axis that critically modifies synaptic physiology and pathophysiology in different contexts in the mature brain and may be a therapeutic target for improving neurophysiological outcomes. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Fn14; Stroke; Synaptic plasticity; Synaptic transmission; TWEAK
语种	英语
scopus关键词	amyloid beta protein; tumor necrosis factor ligand superfamily member 12; tumor necrosis factor receptor superfamily member 12A; animal experiment; animal model; animal tissue; Article; cerebrovascular accident; controlled study; electrophysiology; female; male; mouse; nerve cell plasticity; nerve degeneration; nonhuman; pathophysiology; phosphoproteomics; priority journal; protein phosphorylation; signal transduction; synaptic transmission
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180730
作者单位	Clinical Sciences, Biogen, Cambridge, MA 02142, United States; Biogen Postdoctoral Scientist Program, Cellular Physiology, Biogen, Cambridge, MA 02142, United States; Genetic and Neurodevelopmental Disease Research, Biogen, Cambridge, MA 02142, United States; Chemical Biology and Proteomics, Biogen, Cambridge, MA 02142, United States; Translational Cellular Sciences, Biogen, Cambridge, MA 02142, United States; Comparative Medicine, School of Medicine, Yale University, New Haven, CT 06520, United States
推荐引用方式 GB/T 7714	Nagy D.,Ennis K.A.,Wei R.,et al. Developmental synaptic regulator, TWEAK/Fn14 signaling, is a determinant of synaptic function in models of stroke and neurodegeneration[J],2021,118(6).
APA	Nagy D..,Ennis K.A..,Wei R..,Su S.C..,Hinckley C.A..,...&Burkly L.C..(2021).Developmental synaptic regulator, TWEAK/Fn14 signaling, is a determinant of synaptic function in models of stroke and neurodegeneration.Proceedings of the National Academy of Sciences of the United States of America,118(6).
MLA	Nagy D.,et al."Developmental synaptic regulator, TWEAK/Fn14 signaling, is a determinant of synaptic function in models of stroke and neurodegeneration".Proceedings of the National Academy of Sciences of the United States of America 118.6(2021).