Sindi Ikhlas A, Tannenberg Rudolph K, Dodd Peter R
Centre for Psychiatry and Clinical Neuroscience, School of Medicine, The University of Queensland, Brisbane, Australia.
Centre for Psychiatry and Clinical Neuroscience, School of Medicine, The University of Queensland, Brisbane, Australia; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Neurobiol Aging. 2014 Apr;35(4):746-56. doi: 10.1016/j.neurobiolaging.2013.09.032. Epub 2013 Nov 6.
Synaptic damage is a critical hallmark of Alzheimer's disease, and the best correlate with cognitive impairment ante mortem. Synapses, the loci of communication between neurons, are characterized by signature protein combinations arrayed at tightly apposed pre- and post-synaptic sites. The most widely studied trans-synaptic junctional complexes, which direct synaptogenesis and foster the maintenance and stability of the mature terminal, are conjunctions of presynaptic neurexins and postsynaptic neuroligins. Fluctuations in the levels of neuroligins and neurexins can sway the balance between excitatory and inhibitory neurotransmission in the brain, and could lead to damage of synapses and dendrites. This review summarizes current understanding of the roles of neurexins and neuroligins proteolytic processing in synaptic plasticity in the human brain, and outlines their possible roles in β-amyloid metabolism and function, which are central pathogenic events in Alzheimer's disease progression.
突触损伤是阿尔茨海默病的一个关键标志，也是生前认知障碍的最佳相关指标。突触是神经元之间的通讯位点，其特征是标志性蛋白质组合排列在紧密相邻的突触前和突触后位点。研究最广泛的跨突触连接复合体，它指导突触形成并促进成熟终末的维持和稳定，是突触前神经连接蛋白和突触后神经配蛋白的结合。神经配蛋白和神经连接蛋白水平的波动会影响大脑中兴奋性和抑制性神经传递之间的平衡，并可能导致突触和树突的损伤。本综述总结了目前对神经连接蛋白和神经配蛋白蛋白水解加工在人类大脑突触可塑性中的作用的理解，并概述了它们在β-淀粉样蛋白代谢和功能中的可能作用，而β-淀粉样蛋白代谢和功能是阿尔茨海默病进展中的核心致病事件。
