Dysregulated miRNAs in Progression and Pathogenesis of Alzheimer's Disease.

Abstract

Alzheimer's disease (AD) is a progressive degeneration of neurons due to the accumulation of amyloid-β peptide (Aβ) and hyper-phosphorylation of tau protein in the neuronal milieu leading to increased oxidative stress and apoptosis. Numerous factors contribute towards the progression of AD, including miRNA, which are 22-24 nucleotides long sequence which acts as critical regulators of cellular processes by binding to 3' UTR of mRNA, regulating its expression post-transcriptionally. This review aims to determine the miRNA with the most significant dysregulation in the brain and cerebrospinal fluid (CSF) of human patients. A systemized inclusion/exclusion criterion has been utilized based on selected keywords followed by screening of those articles to conclude a list of 8 highly dysregulated miRNAs based on the fold change of AD vs control patients, which could be used in clinical testing as these miRNAs play central role in the pathophysiology of AD. Furthermore, a network study of highly dysregulated miRNA estimated the association of these miRNA in the mediation of Aβ generation and aggregation, inhibition of autophagy, reduction of Aβ clearance, microglial and astrocytic activation, neuro-inflammation, tau hyper-phosphorylation, and synaptic loss.