Do tau-synaptic long-term depression interactions in the hippocampus play a pivotal role in the progression of Alzheimer's disease?
Zhengtao Hu1
Tomas Ondrejcak2
Pengpeng Yu3
Yangyang Zhang3
Yin Yang4
Igor Klyubin2
Sean P.Kennelly5
Michael J.Rowan2
Neng-Wei Hu4
1.Department of Physiology and Neurobiology,School of Basic Medical Sciences,Zhengzhou University,Zhengzhou,Henan Province,China;Department of Gerontology,The First Affiliated Hospital of Wannan Medical College,Wuhu,Anhui Province,China2.Department of Pharmacology&Therapeutics and Institute of Neuroscience,Trinity College,Dublin,Ireland3.Department of Physiology and Neurobiology,School of Basic Medical Sciences,Zhengzhou University,Zhengzhou,Henan Province,China4.Department of Physiology and Neurobiology,School of Basic Medical Sciences,Zhengzhou University,Zhengzhou,Henan Province,China;Department of Pharmacology&Therapeutics and Institute of Neuroscience,Trinity College,Dublin,Ireland5.Department of Age-Related Healthcare,Tallaght University Hospital,Dublin,Ireland;Department of Medical Gerontology,Trinity College,Dublin,Ireland
摘要：Cognitive decline in Alzheimer's disease correlates with the extent of tau pathology,in particular tau hyperphosphorylation that initially appears in the transentorhinal and related regions of the brain including the hippocampus.Recent evidence indicates that tau hyperphosphorylation caused by either amyloid-β or long-term depression,a form of synaptic weakening involved in learning and memory,share similar mechanisms.Studies from our group and others demonstrate that long-term depression-inducing low-frequency stimulation triggers tau phosphorylation at different residues in the hippocampus under different experimental conditions including aging.Conversely,certain forms of long-term depression at hippocampal glutamatergic synapses require endogenous tau,in particular,phosphorylation at residue Ser396.Elucidating the exact mechanisms of interaction between tau and long-term depression may help our understanding of the physiological and pathological functions of tau/tau(hyper)phosphorylation.We first summarize experimental evidence regarding tau-long-term depression interactions,followed by a discussion of possible mechanisms by which this interplay may influence the pathogenesis of Alzheimer's disease.Finally,we conclude with some thoughts and perspectives on future research about these interactions.
机标关键词：depressionalzheimerroleplaydiseasehippocampusinteractionslong-term
论文发表日期：2023-06-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：7( 1213-1219 )
英文信息