MicroRNA profiling in rat model of neurofibrillary degeneration

Abstract

Neurofibrillary tangles composed of post‐translationally modified protein tau are major hallmarks of neurodegenerative diseases collectively known as tauopathies. Pathogenesis of these disorders is characterized by gene expression changes resulting to altered signalling pathways. Moreover, deregulation of microRNA levels has been also associated with many neurodegenerative diseases, suggesting possible employment of miRNAs as diagnostic biomarkers. In order to identify differentially expressed microRNA molecules during neurofibrillary degeneration we have performed complex miRNA profiling in rat model of tauopathy (expressing human truncated Tau151‐391,4R) that recapitulates major features of neurodegeneration of AD type.Transcriptomic analysis of brain tissue samples showed significantly increased expression of several particular miRNAs involved in the regulation of neuroinflammation (4,1‐fold), innate immune response (2,6‐fold), intracellular trafficking (2,4‐fold) and signal transduction (2,3‐fold). Interestingly, correlation analysis revealed strong positive relationship between dysregulated microRNA molecules.The data suggest that expression of truncated tau protein leads to deregulation of signalling pathways during the neurodegeneration process manifested by altered miRNA expression.Moreover, identified miRNA markers can be potentially applied for the monitoring of the neurodegenerative cascades in Alzheimer's disease and related tauopathies.This work was supported by Research grants: APVV‐0677‐12 and VEGA 2/0141/15 and research grant from Axon Neuroscience SE.