Potential microRNA-related targets in clearance pathways of amyloid-β: novel therapeutic approach for the treatment of Alzheimer’s disease

Abstract

Imbalance between amyloid-beta (Aβ) peptide synthesis and clearance results in Aβ deregulation. Failure to clear these peptides appears to cause the development of Alzheimer’s disease (AD). In recent years, microRNAs have become established key regulators of biological processes that relate among others to the development and progression of neurodegenerative diseases, such as AD. This review article gives an overview on microRNAs that are involved in the Aβ cascade and discusses their inhibitory impact on their target mRNAs whose products participate in Aβ clearance. Understanding of the mechanism of microRNA in the associated signal pathways could identify novel therapeutic targets for the treatment of AD.

MicroRNAs Modulate the Pathogenesis of Alzheimer’s Disease: An In Silico Analysis in the Human Brain

“…In terms of Aβ, different pathways are involved in its clearance, such as the ubiquitin-proteasome system, autophagy, degradation enzymes, and transport across the blood-brain barrier. Different miRNAs are known to modulate components of these pathways, influencing Aβ clearance [ 17 ].…”

“…The overexpression of miR-199 in wildtype mouse embryonic brains altered neurogenesis and neuronal migration [ 58 ]. However, miR-199a-3p can also impair the autophagic process [ 17 ].…”

“…It was already demonstrated in a previous study [ 59 ] and a mouse model of tauopathy [ 60 ]. Moreover, it targets UBE3A , which is involved in AD pathogenesis [ 17 , 61 ].…”

The Ambiguous Role of Microglia in Aβ Toxicity: Chances for Therapeutic Intervention

“…Interestingly, the use of a selective antagomir was able to prevent TREM2 downregulation in a functional assay in murine microglial cells [ 105 ]. In addition, a number of other micro-RNAs have been shown to affect the expression of cell surface molecules necessary for Aβ phagocytosis, such as toll-like receptors (TLR) and scavenger receptors (SR) [ 106 ]. Among these are miR-203, miR-27a, miR-143, miR-19, and miR-146a, involved in TLR modulation and miR-155, miR-185, miR-96, miR-223, and miR-59, involved in SR modulation [ 106 ].…”

“…In addition, a number of other micro-RNAs have been shown to affect the expression of cell surface molecules necessary for Aβ phagocytosis, such as toll-like receptors (TLR) and scavenger receptors (SR) [ 106 ]. Among these are miR-203, miR-27a, miR-143, miR-19, and miR-146a, involved in TLR modulation and miR-155, miR-185, miR-96, miR-223, and miR-59, involved in SR modulation [ 106 ]. The mentioned mechanisms of epigenetic control of microglial function, impacting Aβ clearance, are illustrated in Fig.…”