A hypothesis-generating scoping review of miRs identified in both multiple sclerosis and dementia, their protein targets, and miR signaling pathways.

Cognitive impairment (CI) is a frequent complication affecting people with multiple sclerosis (MS). The causes of CI in MS are not fully understood. Besides MRI measures, few other biomarkers exist to help us predict the development of CI and understand its biology. MicroRNAs (miRs) are relatively stable, non-coding RNA molecules about 22 nucleotides in length that can serve as biomarkers and possible therapeutic targets in several autoimmune and neurodegenerative diseases, including the dementias. In this review, we identify dysregulated miRs in MS that overlap with dysregulated miRs in cognitive disorders and dementia and explore how these overlapping miRs play a role in CI in MS. MiR-15, miR-21, miR-128, miR-132, miR-138, miR-142, miR-146a, miR-155, miR-181, miR-572, and let-7 are known to contribute to various forms of dementia and show abnormal expression in MS. These overlapping miRs are involved in pathways related to apoptosis, neuroinflammation, glutamate toxicity, astrocyte activation, microglial burst activity, synaptic dysfunction, and remyelination. The mechanisms of action suggest that these miRs may be related to CI in MS. From our review, we also delineated miRs that could be neuroprotective in MS, namely miR-23a, miR-219, miR-214, and miR-22. Further studies can help clarify if these miRs are responsible for CI in MS, leading to potential therapeutic targets.