Gene expression in amyotrophic lateral sclerosis: an integrative narrative review of microarray findings, pathogenic mechanisms, and technical challenges

Abstract

Abstract Amyotrophic Lateral Sclerosis (ALS) is a devastating and progressive neurodegenerative disorder with a complex and multifactorial pathogenesis characterized by the loss of upper and lower motor neurons. Despite advances in molecular biology, its pathogenesis remains incompletely understood. This narrative review synthesizes findings from key microarray studies, focusing on dysregulated pathways such as ribosomal function, protein synthesis, and metabolic processes within motor nerves and Schwann cells. We further explore the emerging role of competitive endogenous RNA (ceRNA) networks, particularly those involving long non-coding RNAs (lncRNAs), as revealed by advanced bioinformatics in Alzheimer's disease research. Drawing on this conceptual framework, we discuss how similar regulatory mechanisms might operate in ALS, identifying this as a promising direction for future investigation rather than an established finding. A critical analysis of the technical limitations of microarrays—including small sample sizes, the curse of dimensionality, and challenges in validation—is presented. Finally, we discuss future perspectives, advocating for the integration of microarray data with multi-omics approaches, the application of sophisticated machine learning and deep learning techniques, and the use of distributed computing to overcome current analytical bottlenecks. This integrative approach aims to bridge molecular discoveries with methodological advancements, fostering a deeper understanding of ALS pathogenesis and highlighting novel therapeutic targets.