MicroRNAs in amyotrophic lateral sclerosis: from pathogenetic involvement to diagnostic biomarker and therapeutic agent development

Abstract

MicroRNAs (miRNAs) are a class of endogenous non-coding small single-stranded RNAs that are 21-25 nucleotides (NTs) in length and participate in post-transcriptional gene regulation. Studies have shown that miRNA dysfunction plays a critical role in the occurrence and development of a variety of nervous system diseases, including neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an unclear etiology and is characterized by the selective invasion of motor neurons in the brain and spinal cord. Symptoms can range from mild spasms in the limbs or medulla oblongata muscles to paralysis in almost all skeletal muscles. The role of miRNAs in the pathogenesis, diagnosis, and treatment of ALS has become of greater importance to those studying ALS. In this review, we reviewed experimentally confirmed miRNAs shown to be involved in the pathogenesis of ALS and that are used as diagnostic biomarkers or therapeutic ALS agents. At present, there are at least 20-30 genes clearly related to the pathogenesis of ALS. Multiple miRNAs have been reported in different pathogenic gene models. MiRNAs could be used as biomarkers for the diagnosis of ALS; the differential expression of some miRNAs could be related to ALS prognosis. As therapeutic agents, miRNAs are still in the exploratory stage. Although encouraging results have been achieved using animal models, much research is still needed before clinical trials can ensue. However, with additional miRNA studies in ALS patients and animal models, the pathogenesis, early diagnosis, and therapy of ALS should be elucidated.

Keywords: Amyotrophic lateral sclerosis; Biomarker; Diagnosis; Therapy; microRNAs.