Human Caspases And Neuronal Apoptosis In Neurodegenerative Diseases

Human Caspases and Neuronal Apoptosis in Neurodegenerative Diseases elucidates elaborately the role of caspase enzymes implicated in the initiation of molecular events leading to neuronal apoptosis in the neurodegenerative disease. The book starts with introduction to neuropathology, neurogenetics, and epidemiology of neurodegenerative disease and illustrates the involvement of human caspases, neuronal apoptosis, apoptotic pathways, genetic polymorphisms, and several other factors and underlying mechanisms in the pathology of Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. An important focus in all chapters is the intricate mechanisms and interplay that occur during or leading to neuron death in neurodegenerative diseases, along with disease pathobiology. Provides in-depth knowledge about neurotoxic potential of transition metals, impaired mitochondrial dynamics in the brain neurons, mutant proteins Aß peptide, tau protein, a-synuclein, huntingtin protein and formation of Lewy bodies, reactive oxygen and nitrogen species, ubiquitin proteasome dysregulation, and many others in neurodegenerative diseases Elucidates neurogenetics of gene APP, gene PSEN1, gene APOE, gene LRRK2, gene DJ1, and others in the pathology of neurodegenerative diseases Explains caspases-mediated neuronal apoptosis in pathogenesis of Alzheimer’s disease covering amyloidogenesis, caspase-activated DNase, rho-associated coiled coil–containing protein kinase 1, mammalian sterile 20-like kinase 1, role of synaptic loss, microglial TREM2 receptor, microglial LRP1 receptor, microglial advanced glycation end-product receptor, astrocytic glial a 7 subtypes of nAChR, NLRP3 inflammasome, P2X purinoreceptors, miRNAs, and many other factors Demonstrates the role of caspases and apoptosis in Parkinson’s disease covering truncation of a-synuclein, neuroinflammation, parkin protein, activation of microglial cells, extrinsic and intrinsic pathways of apoptosis, ?tau314, and several other factors Explains etiopathogenesis of Huntington’s disease through covering clinically important topics as role of exon 1 HTT protein, ubiquitous nature of huntingtin, length of expanded polyglutamine tract, classically and alternately activated microglia, nuclear factor kappa B, kynurenine signaling pathway, tumor suppressor protein, PGC-1a gene, advanced glycation end-products, autophagy, and many other significant topics

Four chapters represent the intense current effort to understand the way in which the mitochondrion controls the activation of the final stages of cell death. Another four articles attack the problem from the other side. How do specific insults in particular human or mouse neuro-degenerative diseases translate into mechanisms that will not only allow us to better understand what is happening in these patients but also, with luck, allow for development of more efficient and specific drugs in the future? Firstly, the concept of a central common cell death pathway, originally derived from studies on the nematode, has been an outstanding productive paradigm in bringing together different strands of research. Secondly, truly striking links have been made between results obtained in the culture dish (or even cell-free systems) and the diseased human brain.

As the average life expectancy of many populations throughout the world increases, so to does the incidence of such age-related neurodegenerative disorders as Alzheimer's, Parkinson's, and Huntington's diseases. Rapid advances in our understanding of the molecular genetics and environmental factors that either cause or increase risk for age-related neurodegenerative disor ders have been made in the past decade. The ability to evaluate, at the cellular and molecular level, abnormalities in postmortem brain tissue from patients, when taken together with the development of valuable animal and cell-culture models of neurodegenerative disorders has allowed the identification of sequences of events within neurons that result in their demise in specific neurodegenerative disorders. Though the genetic and environmental factors that pro mote neurodegeneration may differ among disorders, shared biochemical cascades that will ultimately lead to the death of neurons have been identified. These cascades involve oxyradical production, aberrant regulation of cellular ion homeostasis and activation of a stereotyped sequence of events involving mitochondrial dysfunction and activa tion of specific proteases. Pathogenesis of Neurodegenerative Disorders provides a timely compilation of articles that encompasses fundamental mechanisms involved in neurodegenerative disorders. In addition, mechanisms that may prevent age-related neurodegenerative disorders are presented. Each chapter is written by an expert in the particular neurodegenerative disorder or mechanism or neuronal death discussed.

In this revised and expanded second edition, seasoned experts describe in step-by-step detail their best state-of-the-art techniques for studying neuronal cell death. These readily reproducible methods solve a wide variety of research problems, including the detection of the key proteins involved in neuronal apoptosis.

This book highlights the pathophysiological complexities of the mechanisms and factors that are likely to be involved in a range of neuroinflammatory and neurodegenerative diseases including Alzheimer's disease, other Dementia, Parkinson Diseases and Multiple Sclerosis. The spectrum of diverse factors involved in neurodegeneration, such as protein aggregation, oxidative stress, caspases and secretase, regulators, cholesterol, zinc, microglia, astrocytes, oligodendrocytes, etc, have been discussed in the context of disease progression. In addition, novel approaches to therapeutic interventions have also been presented. It is hoped that students, scientists and clinicians shall find this very informative book immensely useful and thought-provoking.

A 2005 survey of the role of apoptosis in the pathogenesis of many significant human illnesses and injury states.

This book examines current knowledge and recent advances in the study of fundamental processes involved in neuronal death, particularly oxidative stress as a causal agent or risk factor. The author presents discussion of oxidative stress in neuronal apoptosis and its role in the neuropathogenesis of age-related neurodegenerative diseases exemplified by Alzheimer's disease, Parkinson's disease and Amyotrophic Lateral Sclerosis.

We organized the Seventh International Winter Conference on Neurodegeneration and Neuroinflammation in a small town of Karuizawa in Nagano Prefecture in Japan on January 20 to 22, 1999. Karuizawa is a nice summer as well as winter resort close to the place for winter Olympic game in the year of 1998. Over 40 scientists gathered together and made hot discussion. Neurodegeneration and neuroinflammation are two major and important neurologic disorders, in which satisfactory neuroprotective and neurorestorative treatment is not available yet. For this purpose, understanding of molecular mechanisms of neuronal cell death in these two disorders is imperative. Recently, pathologic processes common to these two groups of disorders have been identified such as the involvement of inflammatory changes, microglia, cytokines, and apoptosis. We intended to involve scientists working in these two major fields together to participate in hot and fruitful discussion for the understanding of neuronal death and for developing newer methods of treatment. The science is progressing so rapidly today and we are working in a very narrow specialized area. Sometimes, we are ignorant about important discoveries in other fields. This conference was a nice opportunity for scien tists working different areas to meet together and to exchange their experi ence. This volume is the proceedings of this Winter Conference.