Non-coding RNAs in stroke pathology, diagnostics, and therapeutics

Ischemic stroke is a leading cause of death and disability worldwide. Methods to alleviate functional deficits after ischemic stroke focus on restoration of cerebral blood flow to the affected area. However, pharmacological or surgical methods such as thrombolysis and thrombectomy have a narrow effective window. Harnessing and manipulating neurochemical processes of recovery may provide an alternative to these methods. Recently, non-coding RNA (ncRNA) have been increasingly investigated for their contributions to the pathology of diseases and potential for diagnostic and therapeutic applications. Here we will review several ncRNA – H19, MALAT1, ANRIL, NEAT1, pseudogenes, small nucleolar RNA, piwi-interacting RNA and circular RNA – and their involvement in stroke pathology. We also examine these ncRNA as potential diagnostic biomarkers, particularly in circulating blood, and as targets for therapeutic interventions. An important aspect of this is a discussion of potential methods of treatment delivery to allow for targeting of interventions past the blood-brain barrier, including lipid nanoparticles, polymer nanoparticles, and viral and non-viral vectors. Overall, several long non-coding RNA (lncRNA) discussed here have strong implications for the development of pathology and functional recovery after ischemic stroke. LncRNAs H19 and ANRIL show potential as diagnostic biomarkers, while H19 and MALAT1 may prove to be effective therapeutics for both minimising damage as well as promoting recovery. Other ncRNA have also been implicated in ischemic stroke but are currently too poorly understood to make inferences for diagnosis or treatment. Whilst the field of ncRNAs is relatively new, significant work has already highlighted that ncRNAs represent a promising novel investigative tool for understanding stroke pathology, could be used as diagnostic biomarkers, and as targets for therapeutic interventions.