MicroRNAs and synapse turnover in Alzheimer's disease

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.