Abstract：
Alzheimer\'s Disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-beta plaques and neurofibrillary tangles in the brain, leading to synaptic dysfunction and cognitive decline. Healthy synapses are the crucial for normal brain function, memory restoration and other neurophysiological function. Synapse loss and synaptic dysfunction are two primary events that occur during AD initiation. Synapse lifecycle and/or synapse turnover is divided into five key stages and several sub-stages such as synapse formation, synapse assembly, synapse maturation, synapse transmission and synapse termination. In normal state, the synapse turnover is regulated by various biological and molecular factors for a healthy neurotransmission. In AD, the different stages of synapse turnover are affected by AD-related toxic proteins. MicroRNAs (miRNAs) have emerged as critical regulators of gene expression and have been implicated in various neurological diseases, including AD. Deregulation of miRNAs modulate the synaptic proteins and affect the synapse turnover at different stages. In this review, we discussed the key milestones of synapse turnover and how they are affected in AD. Further, we discussed the involvement of miRNAs in synaptic turnover, focusing specifically on their role in AD pathogenesis. We also emphasized the regulatory mechanisms by which miRNAs modulate the synaptic turnover stages in AD. Current studies will help to understand the synaptic life-cycle and role of miRNAs in each stage that is deregulated in AD, further allowing for a better understanding of the pathogenesis of devastating disease.
摘要：
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是大脑中淀粉样蛋白-β斑块和神经原纤维缠结的积累，导致突触功能障碍和认知能力下降。健康的突触对正常的大脑功能至关重要，记忆恢复和其他神经生理功能。突触丧失和突触功能障碍是在AD启动期间发生的两个主要事件。突触生命周期和/或突触周转分为五个关键阶段和几个子阶段，如突触形成，突触组装，突触成熟,突触传递和突触终止。在正常状态下,突触转换受各种生物和分子因素的调节，以实现健康的神经传递。在AD中,突触转换的不同阶段受AD相关毒性蛋白的影响。MicroRNAs（miRNAs）已成为基因表达的关键调节因子，并与各种神经系统疾病有关。包括AD。miRNA的失调调节突触蛋白并影响不同阶段的突触周转。在这次审查中,我们讨论了突触转换的关键里程碑以及它们在AD中的影响。Further,我们讨论了miRNA在突触转换中的参与，特别关注它们在AD发病机制中的作用。我们还强调了miRNA调节AD突触转换阶段的调节机制。目前的研究将有助于理解突触生命周期和miRNA在AD中失调的每个阶段中的作用。进一步允许更好地了解破坏性疾病的发病机制。
