Systems Biology of RNA-Binding Proteins in Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is an adult-onset incurable neurodegenerative disease. Although the precise pathogenesis of ALS remains unknown, mutations in genes encoding RNA-binding proteins (RBPs) have been known as a major culprit. RBPs are involved in almost every aspect of RNA metabolism events from synthesis to degradation. Characteristic features of RBPs in neurodegeneration include misregulation of RNA processing, mislocalization of RBPs to the cytoplasm, and unusual aggregation of RBPs. Modern advancement in technology and computational capabilities suggests an optimistic future for deconvolution of the pathological changes associated with ALS to identify the pathomechanisms of ALS. Importantly, combination of highly multidimensional omic technologies involving proteomics, microarray, and mass spectrometry with computational systems biology approaches provides a systemic methodology to reveal novel mechanisms behind ALS. In this chapter, we begin by summarizing the ALS and involvement of RBPs in ALS. Further, we provide a comprehensive overview of applications of systems biology to study ALS. We imagine that the integration of highly efficient computational tools with multiple omic analyses will help in the discovery of new therapeutic interventions in ALS.