Role of Aβ in Alzheimer’s-related synaptic dysfunction

Synaptic dysfunction is closely related to Alzheimer’s disease (AD) which is also recognized as synaptic disorder. β-amyloid (Aβ) is one of the main pathogenic factors in AD, which disrupts synaptic plasticity and mediates the synaptic toxicity through different mechanisms. Aβ disrupts glutamate rec...

Full description

Saved in:
Bibliographic Details
Published inFrontiers in cell and developmental biology Vol. 10; p. 964075
Main Authors Zhang, Huiqin, Jiang, Xuefan, Ma, Lina, Wei, Wei, Li, Zehui, Chang, Surui, Wen, Jiayu, Sun, Jiahui, Li, Hao
Format Journal Article
LanguageEnglish
Published Frontiers Media S.A 26.08.2022
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary:Synaptic dysfunction is closely related to Alzheimer’s disease (AD) which is also recognized as synaptic disorder. β-amyloid (Aβ) is one of the main pathogenic factors in AD, which disrupts synaptic plasticity and mediates the synaptic toxicity through different mechanisms. Aβ disrupts glutamate receptors, such as NMDA and AMPA receptors, which mediates calcium dyshomeostasis and damages synapse plasticity characterized by long-term potentiation (LTP) suppression and long-term depression (LTD) enhancement. As Aβ stimulates and Ca 2+ influx, microglial cells and astrocyte can be activated and release cytokines, which reduces glutamate uptake and further impair synapse function. Besides, extracellular glutamate accumulation induced by Aβ mediates synapse toxicity resulting from reduced glutamate receptors and glutamate spillovers. Aβ also mediates synaptic dysfunction by acting on various signaling pathways and molecular targets, disrupting mitochondria and energy metabolism. In addition, Aβ overdeposition aggravates the toxic damage of hyperphosphorylated tau to synapses. Synaptic dysfunction plays a critical role in cognitive impairment of AD. The review addresses the possible mechanisms by which Aβ mediates AD-related synaptic impairment from distant perspectives.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-3
content type line 23
ObjectType-Review-1
Reviewed by: Nibaldo C. Inestrosa, Pontificia Universidad Católica de Chile, Chile
Balaji Krishnan, University of Texas Medical Branch at Galveston, United States
P. Hemachandra Reddy, Texas Tech University Health Sciences Center, United States
Edited by: Yuzuru Imai, Juntendo University, Japan
This article was submitted to Molecular and Cellular Pathology, a section of the journal Frontiers in Cell and Developmental Biology
ISSN:2296-634X
2296-634X
DOI:10.3389/fcell.2022.964075