microRNAs Mediate Signaling Pathways in Alzheimer’s Disease: Biomarkers and Therapeutic Targets

microRNAs are extremely small biomolecules that are detected most commonly in intracellular fluid, but also have been found elsewhere in biological fluids. Much of the current literature on the quantitative and qualitative assessment of miRNAs pays particular attention to their critical role in neurodegenerative diseases. There is strong evidence that miRNAs interact with different neuronal signaling pathways to control neuronal homeostasis. Adult neurogenesis dramatically decreases with aging, leading to the impairment of many cognitive functions. In brain samples from Alzheimer’s disease (AD) patients, the expression of one type of miRNA was downregulated but cerebroventricular microinjection of the synthetic miRNA improved the functional deficits. A large body of evidence suggests that miRNAs modulate synaptic plasticity by targeting synaptic receptors or their downstream substrates. miRNAs are vital regulators in long-term memory formation meaning there is a cross-talk between miRNA dysregulation and memory impairment. Compelling evidence demonstrates the existence of a direct link between miRNAs and Aβ synthesis/clearance. A considerable amount of literature has been published on the importance of Tau in AD and indicates that the regulation of Tau protein metabolism occurs in a miRNAs-dependent way. There is a relationship between various miRNAs and increased mitochondrial dysfunction and has been associated with various pathological processes and diseases in the brain including neurodegeneration. Northern blot-based platforms, in situ hybridization, reverse transcription qPCR, microarray, and next-generation sequencing can be considered the most widely used methods for analyzing miRNAs. Overall, the application of miRNAs in the therapeutics of brain diseases is rapidly growing.