Small noncoding RNAs: Pioneering a new therapeutic era in Alzheimer's disease

Alzheimer's disease (AD) is a multifaceted, degenerative neurologic disorder with limited therapeutic options. Only four FDA-approved medications provide mild symptom improvement, and only two qualify as disease-modifying treatments. Recent advances in the understanding of the genetic and molecular bases, including the involvement of non-coding regions, have stimulated interest in small RNA-based therapies. This includes microRNA (miRNA), small interfering RNAs (siRNAs), piwi-associated small RNAs (piRNAs), and transfer RNA-derived small RNAs (tsRNAs). Although promising and increasingly popular in academic and pharmaceutical research, challenges are still formidable. This review provides an extensive overview of the recent findings in AD pathophysiology, novel therapeutic targets, and the development of small size noncoding RNA approaches to overcome the blood-brain barrier. It also provides critical discussion and future perspectives for small non coding RNA-based therapy in AD.