New insights of miRNAs dysregulation in the molecular pathological basis of neurodegenerative sclerosis: A systematic review
Neurodegenerative diseases affect nerve cells, causing impairment in mobility and cognitive abilities, characteristics present in two highly relevant neuropathologies, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). The pathogenesis of these diseases, although distinct, share common neurodegenerative mechanisms. Several studies suggest that miRNAs, small molecules of endogenous non-coding RNA, may assume an important regulatory role in neurodegeneration where their differential expression enables the elucidation of the molecular basis of this process, in addition to offering possible therapeutic targets. We performed a systematic review of the literature through a search in Web of Science, Pubmed/NCBI, and virtual health library (BVS) databases, applying terms indexed in MeSH and DeCS, such as “microRNA”, “amyotrophic lateral sclerosis” and “multiple sclerosis”. We included studies in English, Portuguese, or Spanish, published in the last five years, relating miRNAs associated with pathophysiological pathways of ALS and MS. We excluded studies on non-humans or with polymorphisms in pre-miR genes, duplicated data, or with unavailable data, resulting in a final number of 70 studies included. According to systematic review findings, the families miR-9, miR-23, miR-26, miR-125, miR-133, miR-146, miR-181, miR-206, miR-320, and miR-326 are frequently dysregulated in ALS and MS. The miR-155 and let-7 families are commonly associated with both diseases, regulating genes involved in mechanisms such as neuroinflammation, neurogenesis, and cell differentiation. The elucidation of the newest miRNAs and their main pathways may assist in the characterization of the molecular basis of these diseases, mainly involving those associated with pro-inflammatory processes, microglia activation, and neuronal death, mechanisms associated with ALS. They also can involve myelin breakdown mechanisms, astrocyte damage, and neuronal death, which are related to MS. These molecular markers may help determine biomarkers for amyotrophic lateral sclerosis and multiple sclerosis.