Chapters authored
Pathological Interaction between DNA Repair and Mitochondrial Dysfunction in ALS
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of cortical and spinal cord motor neurons. Several mechanisms have been implicated in the pathogenesis of the disease, including mitochondrial dysfunction, oxidative stress, and genome instability. Recently, a combined role between impaired DNA repair and subsequent mitochondrial dysfunction has emerged as a novel pathological interaction in neurodegeneration. This is exemplified by mutations in the RNA-/DNA-binding proteins FUS and TDP-43 as well as superoxide dismutase 1 (SOD1) gene, all related to familial ALS. In this regard, evidence supports either downregulation or impaired recruitment of DNA repair enzymes in both nuclear and mitochondrial genomes. In addition, evidence also suggests a complex metabolic dysregulation as a critical component in the promotion of the disease. This chapter aims to integrate the molecular mechanisms of this pathological interplay and the possible role in cytosolic protein aggregation and cell death in motor neurons.
Part of the book: Amyotrophic Lateral Sclerosis