Proper folding of proteins is crucial for cell function. Chaperones and enzymes that post-translationally modify newly synthesized proteins help ensure that proteins fold correctly, and the unfolded protein response functions as a homeostatic mechanism that removes misfolded proteins when cells are stressed. This book covers the entire spectrum of proteostasis in healthy cells and the diseases that result when control of protein production, protein folding, and protein degradation goes awry.
This book bridges the gap between fundamental research and biomedical and pharmacological applications on proteases. It represents a comprehensive overview of the multifaceted field of proteases in cellular environment and highlights the recently elucidated functions of complex proteolytic systems in different diseases. Several established investigators have elucidated the crucial role of proteases in biological processes, including how proteolytic function and regulation can be combined to develop new strategies of therapeutic interventions. Proteases form one of the largest and most diverse families of enzymes known. It is now clear that proteases are involved in every aspect of life functions of an organism. Under physiological conditions, proteases are regulated by their endogenous inhibitors; however, when the activity of proteases is not regulated appropriately, disease processes can result in. So, there is absolute need for a stringent control of proteolytic activities in cells and tissues. Dysregulation of proteases may cause derangement of cellular signalling network resulting in different pathophysiological conditions such as vascular remodelling, atherosclerotic plaque progression, ulcer and rheumatoid arthritis, Alzheimer disease, cancer metastasis, tumor progression and inflammation. Additionally, many infective microorganisms require proteases for replication or use proteases as virulence factors, which have facilitated the development of protease-targeted therapies for a variety of parasitic diseases.
Using a multidisciplinary approach, this book describes the biochemical mechanisms associated with dysregulation of proteases and the resulting pathophysiological consequences. It highlights the role and regulation of different types of proteases as well as their synthetic and endogenous inhibitors. The role of proteases was initially thought to be limited to general metabolic digestion. However, we now know that the role of protein breakdown is much more complex, and proteases have multiple functions: they are coupled to turnover and can affect protein composition, function and synthesis. In addition to eliminating abnormal proteins, breakdown has many modulatory functions, including activating and inactivating enzymes, modulating membrane function, altering receptor channel properties, affecting transcription and cell cycles and forming active peptides. The ubiquity of proteases in nature makes them an important target for drug development. This in-depth, comprehensive is a valuable resource for researchers involved in identifying new targets for drug development. With its multidisciplinary scope, it bridges the gap between fundamental and translational research in the biomedical and pharmaceutical industries, making it thought-provoking reading for scientists in the field.
In aerobic tissues such as heart, brain, kidney, liver and brown fat, mitochon dria account for more than 20% of cell protein and play an essential role in res piration, ATP formation, ketogenesis, gluconeogenesis, amino acid metabolism, ureagenesis, thermogenesis and a variety of other metabolic activities. The mecha nisms by which these activities are integrated and regulated within the overall context of cellular physiology is of much current research interest. In order to bring together scientists examining the various diverse aspects of this overall pro blem, an International Conference on INTEGRATION OF MITOCHONDRIAL FUNC TION was held June 4-7, 1987 at the Hanes Art Center on the campus of the Uni versity of North Carolina at Chapel Hill. The chapters of this volume derive from presentations made at this conference. The focus of INTEGRATION OF MITOCHONDRIAL FUNCTION is on signifi cant new experimental and theoretical advances concerning integration of mito chondrial function at the organelle, cell, tissue and whole organism levels of organization.
Methods in Toxicology, Volume 2: Mitochondrial Dysfunction provides a source of methods, techniques, and experimental approaches for studying the role of abnormal mitochondrial function in cell injury. The book discusses the methods for the preparation and basic functional assessment of mitochondria from liver, kidney, muscle, and brain; the methods for assessing mitochondrial dysfunction in vivo and in intact organs; and the structural aspects of mitochondrial dysfunction are addressed. The text also describes chemical detoxification and metabolism as well as specific metabolic reactions that are especially important targets or indicators of damage. The methods for measurement of alterations in fatty acid and phospholipid metabolism and for the analysis and manipulation of oxidative injury and antioxidant systems are also considered. The book further tackles additional methods on mitochondrial energetics and transport processes; approaches for assessing impaired function of mitochondria; and genetic and developmental aspects of mitochondrial disease and toxicology. The text also looks into mitochondrial DNA synthesis, covalent binding to mitochondrial DNA, DNA repair, and mitochondrial dysfunction in the context of developing individuals and cellular differentiation. Microbiologists, toxicologists, biochemists, and molecular pharmacologists will find the book invaluable.
Mitochondria are subcellular organelles evolved by the endosymbiosis of bacteria with eukaryotic cells. They are the main source of ATP in the cell and engaged in other aspects of cell metabolism and cell function, including the regulation of ion homeostasis, cell growth, redox status, and cell signaling. Due to their central role in cell life and death, mitochondria are also involved in the pathogenesis and progression of human diseases/conditions, including neurodegenerative and cardiovascular disorders, cancer, diabetes, inflammation, and aging. However, despite the increasing number of studies, precise mechanisms whereby mitochondria are involved in the regulation of basic physiological functions, as well as their role in the cell under pathophysiological conditions, remain unknown. A lack of in-depth knowledge of the regulatory mechanisms of mitochondrial metabolism and function, as well as interplay between the factors that transform the organelle from its role in pro-survival to pro-death, have hindered the development of new mitochondria-targeted pharmacological and conditional approaches for the treatment of human diseases. This book highlights the latest achievements in elucidating the role of mitochondria under physiological conditions, in various cell/animal models of human diseases, and in patients.
Mitochondrial Neuropathies, Volume 146, brings together experts in a range of diseases that damage the nervous system to present the role of mitochondrial dysfunction in their particular field, with this new release focusing on Mitochondrial dysfunction in Alzheimer's Disease, HIV and the mitochondrial: immune interface in the CNS, The Impact of mitochondrial damage in HIV-induced peripheral neuropathy, Mitochondrial dysfunction and the pathogenesis of chemotherapy-induced peripheral neuropathy, Disorders of mitochondrial biogenesis in peripheral neuropathy, Mitochondrial dysfunction and the pathogenesis of diabetic neuropathy, Manipulating mitochondria to treat peripheral neuropathy, and DCA therapy - the yin and yang of mitochondrial activation. - Contains contributions from a diverse group of experts - Presents a timely resource that brings together different fields to highlight a common pathogenic mechanism - Focuses on the role of mitochondria in diverse neuropathies
Mitochondria are critical to the survival of cells, therefore, it is not surprising that abnormalities in mitochondrial function may lead to human disease. This book concentrates on the biology and pathology of mitochondria, covering some ot the important basic science features of the biology of mitochondria. It then moves on to discuss the breadth of human diseases related to mitochondrial dysfunction, including Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), and Alzheimer's disease.* Provides comprehensive coverage of basic science and clinical features of mitochondrial dysfunction* Presents detailed analysis of "hot" topics in mitochondrial function and neurodegenerative diseases* Includes outstanding list of contributing authors
