MIRNA-22 3p AND ITS ROLE IN TAU PHOSPHORYLATION

Abstract

Neurodegenerative disorders occur when neurons, in the brain and spinal cord, begin to decline. Instabilities in these cells cause them to function irregularly and eventually result in death. A subset of these diseases is called tauopathies. Tauopathies are characterized by a filamentous accumulation of hyper-phosphorylated tau, in neurons and glial cells. Currently, it is unknown how tau becomes hyper-phosphorylated and/or it accumulates in the brain. Tau is a highly soluble natively unfolded protein, closely associated with the proper functioning of the cytoskeletal network. However, in tauopathies, tau becomes an insoluble protein that forms intracellular fibrillar deposits in neurons and glial cells. Studies have shown that there is a direct relationship between the abnormal increase in tau phosphorylation, the cell cycle, and MiRNA-22-3p. There have been several strategies and targets developed in order to treat tauopathies, but there are no known consistent, effective treatments. Recently, miRNAs have emerged as a potential target to manipulate the tau protein. MiRNAs are small noncoding RNAs, that control major cellular functions by binding to the 3’ untranslated region of messenger RNAs, causing inhibition of their translation or promoting their degradation. We have hypothesized that miRNA-22-3p halts abnormal tau phosphorylation levels, in brain endothelial cells. To test this hypothesis, we transfected a miRNA-22-3p mimic, into a brain endothelial cell line. Then, we ran a western blot experiment to look at the proteins, related to tau. We looked at total tau, tau phosphorylation at different epitopes, and P21, a cell cycle marker. Our data demonstrated that miRNA-22-3p halts abnormal tau phosphorylation. In conclusion, we have shown a relationship between miRNA-22-3p and tau phosphorylation. We have highlighted a possible therapeutic benefit that, when investigated further, could serve as a potential treatment on tauopathies and accentuated favorable targets against abnormal tau phosphorylation. We hope to be able to provide others with the information needed to manipulate miRNA-22-3p and downregulate the expression of the tau protein.