Abstract
Multi-pathway approaches for the treatment of complex polygenic disorders are emerging as alternatives to classical monotarget therapies and microRNAs are of particular interest in that regard. MicroRNA research has come a long way from their initial discovery to the cumulative appreciation of their regulatory potential in healthy and diseased brain. However, systematic interrogation of putative therapeutic or toxic effects of microRNAs in (models of) Alzheimer’s disease is currently missing and fundamental research findings are yet to be translated into clinical applications. Here, we review the literature to summarize the knowledge on microRNA regulation in Alzheimer’s pathophysiology and to critically discuss whether and to what extent these increasing insights can be exploited for the development of microRNA-based therapeutics in the clinic.
Highlights
Multi-pathway approaches for the treatment of complex polygenic disorders are emerging as alternatives to classical monotarget therapies and microRNAs are of particular interest in that regard
Network biology and multi-modal therapies begin to attract attention in Alzheimer’s disease (AD) research [10, 13, 17, 18]. miRNAtargeted therapeutics are suited for such purposes, as they regulate multiple components of several molecular cascades converging on disease-relevant patho-phenotypes
The field of miRNA-based therapeutics is developing in the slipstream of other oligonucleotide-based therapeutics
Summary
Often easy dosing, such as oral administration Can target extracellular and intracellular targets Some can cross the BBB Combination therapy possible/ ongoing Faster clearance than mAbs, good to avoid some side-effects Stable 'One-drug, one target' Specificity can be dependent on binding-site, affinity, etc.
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