MicroRNA as a Potential Biomarker for Amyotrophic Lateral Sclerosis (ALS)

Background: Amyotrophic lateral sclerosis (ALS) is a rare, incurable, and fatal neurodegenerative disease that affects the muscles and results in paralysis. The onset and development of ALS involve complex interactions among metabolic signaling, genetic pathways, and external factors (epigenetics). New biomarkers and alternative therapeutic targets have been suggested; nonetheless, the results have been unsatisfactory. Mutations in SOD1, fused in sarcoma (FUS), and TAR DNA-binding protein 43 (TDP-43) have been identified in sporadic amyotrophic lateral sclerosis and approximately 12–20% of familial amyotrophic lateral sclerosis (fALS). Aim: This review analyzes dysregulated microRNA signaling pathways and their interactions with metabolic pathways in the context of ALS progression. Significance: Despite this, biomarkers remain unreliable, and the current medications prolong life without providing a cure. Some proposed approaches to control ALS progression include balancing autophagy and apoptosis, eliminating aggregated proteins, addressing mitochondrial dysfunction, and reducing inflammation. There is a need for studies on new biomarkers, medications, and therapeutic targets. In this context, deregulated circulating microRNAs are attracting attention for new studies on ALS at various phases of the disease. Despite the extensive literature on microRNAs as potential biomarkers for ALS, the proposition for translational clinical use remains limited. Studies have indicated a significant downregulation or upregulation of microRNAs in the motor neurons of ALS patients compared with those with other neurodegenerative disorders and healthy controls. The microRNA biogenesis highlights the importance of this study. MicroRNAs regulate protein synthesis (translation); all human cells express many microRNAs. The complementary structures of microRNA sequences and their mRNA targets allow them to significantly alter cellular and physiological processes. Studies have examined these microRNAs as potential biomarkers for several physiological states and diseases. Comments: The success of these studies may lead to simple, low-cost, and efficient solutions for controlling the progression of ALS and other degenerative diseases. As a result, it is challenging to identify a specific biomarker with total reliability, as a specific microRNA that is increased in one disease phase can decrease in another. These points require careful consideration. They exhibit several complexities and varied interactions, focusing on mRNA targets. The current critical review highlights the potential of microRNAs as biomarkers for diagnosis, prognosis, and therapeutic options in ALS, and raises several points for discussion. Conclusions: The current critical review highlights the potential of microRNAs as biomarkers for diagnosis, prognosis, and therapeutic options in ALS, and raises several points for discussion.