About the book
The groundbreaking discoveries in 2006 implicating aggregation /fibrillation of the RNA/DNA-binding protein TDP-43 and FUS in amyotrophic lateral sclerosis (ALS) triggered a flurry of research activities towards understanding the neurobiology and pathology of these RNA/DNA binding proteins. Involvement of dozen additional factors including C9ORF72, profilin etc were subsequently reported, however, how these factors trigger neuronal apoptosis still remains unclear, which is a roadblock for developing newer therapeutics. Whether neurotoxicity of RNA/DNA binding proteins in ALS is due to its ‘gain-of-toxicity’ or ‘loss-of-function’ is a key question. While initial research focused on the RNA processing defects, recent studies demonstrated a widespread imbalance in genome damage versus repair, opening avenues for potential DNA repair based therapeutics. Despite significant increase in our understanding of the pathological and biochemical changes in ALS, there is no current cure; available treatments only temporarily slow the disease progression, but do not prevent neuronal death. This underscores the necessity of an overarching approach to unravel the fundamental mechanisms of disease initiation and progression in order to design effective ways develop improved treatment protocols for ALS patients. This book is intended to debate recent advances in our understanding of ALS group of diseases and outline future direction for research activities towards finding a cure for these debilitating brain diseases.