Aggregates of the TAR DNA binding protein 43 (TDP-43), are hallmark features of the neurodegenerative diseases Amyotrophic Lateral Sclerosis (ALS) and frontotemporal dementia (FTD), with overlapping clinical, genetic and pathological features. TDP-43 and Neurodegeneration: From Bench to Bedside summarizes new findings in TDP-43 pathobiology and proteinopathies. The book summarizes TDP-43's structure, function, biology, misfolding, aggregation, pathogenesis and therapeutics. It includes autophagy-mediated therapy, role of stress granule, novel genetic, cell culture-based models, systems biology for precision medicine, development of stem cells and mechanism-based therapies that can target ALS and other related neurodegenerative diseases. This book is written for neuroscientists, neurologists, clinicians, advanced graduate students, drug discovery researchers, as well as cellular and molecular biologists involved in ALS, motor neuron disease (MND) and other neurodegenerative disorders.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective death of subsets of motorneuorn (MN) populations in the brainstem and spinal cord with signature hallmarks of mitochondrial Ca2+ overload, homeostasis dysregulation, excitotoxicity, impaired axonal transport, muscle weakness and paralysis. Although disruptions of cytosolic and mitochondrial Ca2+ (in particular low ( Ca2]]i) buffering and a strong interaction between metabolic mechanisms and Ca2]]i) have been associated with selective motoneuron degeneration, the underlying mechanisms are not well understood. The present evidence supports a hypothesis that mitochondria are a primary target of SOD1-mediated toxicity in ALS, and intracellular alterations of cytosolic and mitochondria-ER microdomain calcium accumulation might aggravate the course of this neurodegenerative disease. This book aims to provide an overview of the known players and their interactions, their role in the selective MN loss, recent advances in this field and a detailed discussion about what has been learned about Ca2+ homeostasis and the role of mitochondria in MNs in pathophysiological conditions.