Factors affecting the GABAergic synapse function in Alzheimer’s disease: Focus on microRNAs

Alzheimer's disease (AD) is a progressive neurological disease characterized by the loss of cognitive function, confusion, and memory deficit. Accumulation of abnormal proteins, amyloid beta (Aß), and phosphorylated Tau (p-tau) forms plaques and tangles that deteriorate synapse function, resulting in neurodegeneration and cognitive decline in AD. The human brain is composed of different types of neurons and/or synapses that are functionally defective in AD. The GABAergic synapse, the most abundant inhibitory neuron in the human brain was found to be dysfunctional in AD and contributes to disrupting neurological function. This study explored the types of GABA receptors associated with neurological dysfunction and various biological and environmental factors that cause GABAergic neuron dysfunction in AD, such as Aβ, p-tau, aging, sex, astrocytes, microglia, APOE, mental disorder, diet, physical activity, and sleep. Furthermore, we explored the role of microRNAs (miRNAs) in the regulation of GABAergic synapse function in neurological disorders and AD states. We also discuss the molecular mechanisms underlying GABAergic synapse dysfunction with a focus on miR-27b, miR-30a, miR-190a/b, miR-33, miR-51, miR-129-5p, miR-376-3p, miR-376c, miR-30b and miR-502-3p. The purpose of our article is to highlight the recent research on miRNAs affecting the regulation of GABAergic synapse function and factors that contribute to the progression of AD.