The Application of RNA Sequencing in Understanding the Molecular Mechanisms and Therapeutic Potential in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive loss of motor neurons, leading to muscle weakness and paralysis. While significant advances have been made in understanding the pathophysiology of ALS, there is still no curative treatment, and the underlying molecular mechanisms remain incompletely understood. RNA sequencing (RNA-seq) has emerged as a powerful tool to analyze the transcriptome, providing critical insights into gene expression changes, alternative splicing events, and RNA metabolism. This review highlights the application of RNA-seq in ALS research, including its use in identifying ALS-related gene mutations and differential gene expressions. Key findings include the role of C9orf72, SOD1, FUS, TARDBP, and UBQLN2 mutations in disease progression, as well as the identification of potential biomarkers in cerebrospinal fluid and peripheral blood samples. Additionally, novel RNA-seq technologies, such as single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics, are explored for their ability to capture the heterogeneity of cellular populations and unravel the complex molecular mechanisms underlying ALS. Despite the promise of RNA-seq, several technical, analytical, and ethical challenges must be addressed to fully realize its potential in ALS research. Future directions include integrating RNA-seq data with other multi-omics approaches, advancing personalized medicine, and applying emerging sequencing technologies. Overall, RNA-seq continues to play a pivotal role in uncovering the molecular mechanisms of ALS and holds promise for the development of targeted therapies.