Autophagy Of The Nervous System

What is autophagy? Why would neurons digest parts of themselves through autophagy? How can autophagy save the lives of cells under some conditions, but act as an accomplice to cell death in others? By what mechanisms are autophagy-related processes dysregulated in neurological diseases, and are there therapeutic strategies to correct or compensate for their dysfunction? This book provides an expert view of major concepts in autophagy research with a focus on autophagy in neurons. Experimental evidence for evolutionarily conserved and specialized regulatory mechanisms for autophagy in the mammalian nervous system will be presented, including recent data on braking mechanisms. Areas of intersection with cell death, the ubiquitin-proteasome system, chaperone-mediated autophagy, and the endocytic pathway will be reviewed, along with emerging areas of mitochondrial autophagy (mitophagy) and the autophagic regulation of neuritic/synaptic processes. Advances in delineating mechanisms by which autophagy is involved in the pathophysiology of neurological disorders, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, ischemia/hypoxia and lysosomal storage diseases, will be discussed along with current drug development strategies targeting autophagy.

Autophagy in Health and Disease, Second Edition provides a comprehensive overview of the process of autophagy and its impact on human physiology and pathophysiology. It expands on the scope of the first edition by covering a wider range of cell types, developmental processes, and organ systems. The second edition is an international effort by investigators from 15 different countries whose many contributions are comprised in 28 chapters organized into six sections. The first section (Chapters 1-7) covers foundational concepts, including history, trajectory of the research field, mechanisms of autophagy, and autophagy regulation. The second section (Chapters 8-11) details developmental aspects, including stem cells, embryogenesis, hematopoiesis, and paligenosis. The subsequent sections are devoted to the role of autophagy in specific organ systems involved in metabolic control and diabetes (Chapters 12-15), the cardiovascular system (Chapters 16-18), and the nervous system (Chapters 19-20). The final section (Chapters 21-28) addresses autophagy in other organ systems vital to human health and longevity. Also included are chapters on microautophagy, chaperone-mediated autophagy, and the potential for autophagy as a therapeutic target. Autophagy in Health and Disease is invaluable to anyone new to the field as well as established investigators looking for a broader understanding of autophagy from outside their specific field of study. Provides a comprehensive overview of the process of autophagy and its impact on human physiology and pathology Offers extended coverage of the mechanisms that mediate autophagy Covers the role of autophagy in stem cells and induced pluripotent stem cells, as well as the regenerative process of paligenosis Highlights important questions that remain to be addressed

Comprehensive overview of different aspects of autophagy as it relates to neurodegenerative diseases. The pathogenesis of the main neurodegenerative disorders includes either the accumulation of altered or misfolded proteins or exposure to several toxics. Autophagy constitute one of the two principal cellular pathways implicate in the clearance of these material and can serve as a neuroprotective mechanism. Topics include: the role of autophagy in the brain, the role of autophagy in the principal neurodegenerative disorders, and the mechanism by which different molecules cause neurotoxicity and the role autophagy plays.

Peripheral neuropathy includes a wide range of diseases affecting millions around the world, and many of these diseases have unknown etiology. Peripheral neuropathy in diabetes represents a large proportion of peripheral neuropathies. Nerve damage can also be caused by trauma. Peripheral neuropathies are a significant clinical problem and efficient treatments are largely lacking. In the case of a transected nerve, different methods have been used to repair or reconstruct the nerve, including the use of nerve conduits, but functional recovery is usually poor. Autophagy, a cellular mechanism that recycles damaged proteins, is impaired in the brain in many neurodegenerative diseases affecting animals and humans. No research, however, has investigated the presence of autophagy in the human peripheral nervous system. In this study, I present the first structural evidence of autophagy in human peripheral nerves. I also show that the density of autophagy structures is higher in peripheral nerves of patients with chronic idiopathic axonal polyneuropathy (CIAP) and inflammatory neuropathy than in controls. The density of these structures increases with the severity of the neuropathy. In animal model, using Goto-Kakizaki (GK) rats with diabetes resembling human type 2 diabetes, activation of autophagy by local administration of rapamycin incorporated in collagen conduits that were used for reconnection of the transected sciatic nerve led to an increase in autophagy proteins LC3 and a decrease in p62 suggesting that the autophagic flux was activated. In addition, immunoreactivity of neurofilaments, which are parts of the cytoskeleton of axons, was increased indicating increased axonal regeneration. I also show that many proteins involved in axonal regeneration and cell survival were up-regulated by rapamycin in the injured sciatic nerve of GK rats four weeks after injury. Taken together, these findings provide new knowledge about the involvement of autophagy in neuropathy and after peripheral nerve injury and reconstruction using collagen conduits.

What is autophagy? Why would neurons digest parts of themselves through autophagy? How can autophagy save the lives of cells under some conditions, but act as an accomplice to cell death in others? By what mechanisms are autophagy-related processes dysregulated in neurological diseases, and are there therapeutic strategies to correct or compensate for their dysfunction? This book provides an expert view of major concepts in autophagy research with a focus on autophagy in neurons. Experimental evidence for evolutionarily conserved and specialized regulatory mechanisms for autophagy in the mammalian nervous system will be presented, including recent data on braking mechanisms. Areas of intersection with cell death, the ubiquitin-proteasome system, chaperone-mediated autophagy, and the endocytic pathway will be reviewed, along with emerging areas of mitochondrial autophagy (mitophagy) and the autophagic regulation of neuritic/synaptic processes. Advances in delineating mechanisms by which autophagy is involved in the pathophysiology of neurological disorders, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, ischemia/hypoxia and lysosomal storage diseases, will be discussed along with current drug development strategies targeting autophagy.

Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging is an eleven volume series that discusses in detail all aspects of autophagy machinery in the context of health, cancer, and other pathologies. Autophagy maintains homeostasis during starvation or stress conditions by balancing the synthesis of cellular components and their deregulation by autophagy. This series discusses the characterization of autophagosome-enriched vaccines and its efficacy in cancer immunotherapy. Autophagy serves to maintain healthy cells, tissues, and organs, but also promotes cancer survival and growth of established tumors. Impaired or deregulated autophagy can also contribute to disease pathogenesis. Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and forward-thinking, these books offer a valuable guide to cellular processes while also inciting researchers to explore their potentially important connections. Presents the most advanced information regarding the role of the autophagic system in life and death Examines whether autophagy acts fundamentally as a cell survivor or cell death pathway or both Introduces new, more effective therapeutic strategies in the development of targeted drugs and programmed cell death, providing information that will aid in preventing detrimental inflammation Features recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities, including atherosclerosis and CNS tumors, and their development and treatment Includes chapters authored by leaders in the field around the globe—the broadest, most expert coverage available

Cell Cycle in the Central Nervous System overviews the changes in cell cycle as they relate to prenatal and post natal brain development, progression to neurological disease or tumor formation.Topics covered range from the cell cycle during the prenatal development of the mammalian central nervous system to future directions in postnatal neurogenesis through gene transfer, electrical stimulation, and stem cell introduction. Additional chapters examine the postnatal development of neurons and glia, the regulation of cell cycle in glia, and how that regulation may fail in pretumor conditions or following a nonneoplastic CNS response to injury. Highlights include treatments of the effects of deep brain stimulation on brain development and repair; the connection between the electrophysiological properties of neuroglia, cell cycle, and tumor progression; and the varied immunological responses and their regulation by cell cycle.