Mitochondrial Dysfunction
Mitochondrial Dysfunction

Author: Lawrence H. Lash

Publisher: Elsevier

Published: 2013-10-22

Total Pages: 527

ISBN-13: 1483218619

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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.

Organelle Contact Sites
Organelle Contact Sites

Author: Mitsuo Tagaya

Publisher: Springer

Published: 2017-08-16

Total Pages: 254

ISBN-13: 9811045674

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This book provides the first comprehensive coverage of the quickly evolving research field of membrane contact sites (MCS). A total of 16 chapters explain their organization and role and unveil the significance of MCS for various diseases. MCS, the intracellular structures where organellar membranes come in close contact with one another, mediate the exchange of proteins, lipids, and ions. Via these functions, MCS are critical for the survival and the growth of the cell. Owing to that central role in the functioning of cells, MCS dysfunctions lead to important defects of human physiology, influence viral and bacterial infection, and cause disease such as inflammation, type II diabetes, neurodegenerative disorders, and cancer. To approach such a multifaceted topic, this volume assembles a series of chapters dealing with the full array of research about MCS and their respective roles for diseases. Most chapters also introduce the history and the state of the art of MCS research, which will initiate discussion points for the respective types of MCS for years to come. This work will appeal to all cell biologists as well as researchers on diseases that are impacted by MCS dysfunction. Additionally, it will stimulate graduate students and postdocs who will energize, drive, and develop the research field in the near future.

Mitochondria and Endoplasmic Reticulum Dysfunction in Parkinson’s Disease
Mitochondria and Endoplasmic Reticulum Dysfunction in Parkinson’s Disease

Author: Sandeep Kumar Barodia

Publisher: Frontiers Media SA

Published: 2020-01-23

Total Pages: 132

ISBN-13: 2889633349

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Several pathogenic mechanisms are involved in the pathogenesis of Parkinson’s Disease (PD), a neurodegenerative disease characterized by the loss of substantial nigra (SN) dopamine (DA) neurons. Alterations in calcium (Ca2+) homeostasis, cellular proteostasis, axonal transport, mitochondrial function, and neuroinflammation are linked to PD. However, research involving inter-organelle communication and their significance as precise mechanisms underlying neuronal death in PD remain to be elucidated. Evidence showed that perturbations in the mitochondria-endoplasmic reticulum (ER) network play an important role in the pathogenesis of PD. Alterations in the mitochondria-ER interface have been reported in PARK2 knockout mice and patients harboring PARK2 mutations. Enhanced parkin levels maintain mitochondria-ER cross-talk and assure regulated Ca2+ transfer to sustain cell bioenergetics. Several familial PD-related proteins, including Parkin and PINK1, may lead to modifications in the mitochondria-ER signaling. Interestingly, mitochondria-ER tethering suppresses mitophagy and parkin/PINK1-dependent mechanism regulates the destruction of mitochondria-ER contact sites by catalyzing a rapid burst of Mfn2 phospho-ubiquitination to trigger p97-dependent disassembly of Mfn2 complexes from the outer mitochondrial membrane. Mitofusin-mediated ER stress elicited neurodegeneration in Pink1/Parkin models of PD. α-Synuclein, a presynaptic protein, can bind to the ER-mitochondria tethering protein vesicle-associated membrane protein-associated protein B (VAPB) to disrupt Ca2+ homeostasis and mitochondrial ATP production. It has been reported that ER stress and mitochondrial cell death pathways might mediate A53T mutant α-synuclein-induced toxicity. Mitochondria-ER signaling mechanism is poorly characterized in neurons and its association in neuronal pathophysiology remains uncertain. The presence of mitochondria-ER contacts in neurons, preferentially at synapses, suggests a potential role in regulating synaptic activity. Alterations in mitochondria-ER associations are expected to be potentially detrimental to neurons, especially to SN DA neurons. Compounds from an unbiased chemical screen reverse both ER-to-Golgi trafficking defects and associated mitochondrial dysfunction in different PD models. In addition, a dibenzoylmethane derivative protects DA neurons against ER stress. Thus, mitochondria-ER signaling may represent a possible upstream drug target as potential therapeutic strategy for PD. In this Research Topic, we bring together knowledge that emphasizes the importance of mitochondria-ER communication and its impact to further dissect the pathogenic mechanisms in PD.

Reviews on New Drug Targets in Age-Related Disorders
Reviews on New Drug Targets in Age-Related Disorders

Author: Paul C. Guest

Publisher: Springer Nature

Published: 2021-03-16

Total Pages: 274

ISBN-13: 3030550354

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Aging is an inevitable part of life, and is becoming a worldwide social, economic and health problem due to the fact that an increasing proportion of individuals in the advanced age category have a higher probability of developing age-related disorders. New therapeutic approaches are still in need to decrease or slow the effects of such diseases in this aging society. Advances in ‘omic technologies such as genomics, transcriptomics, proteomics and metabolomics have significantly advanced our understanding of diseases in multiple medical areas. It is hoped that emerging hits from these analyses might be prioritized for further screening as potential novel drug targets for increasing the human healthspan in line with the lifespan, which will in turn lead to new therapeutic strategies and drug development projects by the pharmaceutical industry. This new book presents a series of reviews describing studies which have resulted in the identification of potential new drug targets for age-related disorders. Much of this information has come from ‘omic comparisons of healthy and disease states or from testing the effects of potential new therapeutic approaches. Each chapter will be presented in the context of specific chronic diseases or different therapeutic strategies, providing important information on disease mechanisms related to the aging process. This book will be of interest to researchers in the areas of aging and chronic disease, as well as clinical scientists, physicians, and major drug companies. With contributors from Australia, Brazil, Canada, France, Germany, India, Iran, Iraq, South Africa, South Korea, Thailand, Ukraine, United Kingdom, United States of America, Uruguay and Vietnam, this is a timely follow up to Guest’s previous book Reviews on New Drug Targets in Age-Related Disorders.

Parkinson's Disease
Parkinson's Disease

Author: Patrik Verstreken

Publisher: Academic Press

Published: 2016-12-19

Total Pages: 332

ISBN-13: 0128038055

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Parkinson's Disease: Molecular Mechanisms Underlying Pathology explores the molecular pathways at the basis of the cellular defects connected to Parkinson's disease, the second most common neurodegenerative disease, and the most common movement disorder. This book presents the latest research on the pathways and mechanisms that have been discovered to play a role in Parkinson's pathology. This focus on mechanisms rather than individual genes allows the contributors to elaborate on overlapping and joint functions of different causative genes. Readers will find descriptions of model systems that present parallels (and differences) between discoveries in different species, demonstrating the importance of multidisciplinary research that spans a broad array of technologies and model organisms. Written from both a cross-methodology and cross-species perspective, the book provides readers with the current state of knowledge on the molecular biology of Parkinson's. - Written by experts in the field that focus on pathways and mechanisms implicated in Parkinson's pathology - Draws parallels between multidisciplinary discoveries in different model organisms using an array of technologies - Provides a cross-methodology and cross-species approach to understanding the molecular biology of Parkinson's disease - Includes approximately 25 color Illustrations and diagrams to explain concepts and models - Focuses on key pathways and mechanisms (as opposed to model organism or gene) to provide a multidisciplinary approach to Parkinson's disease

The Case of the Frozen Addicts
The Case of the Frozen Addicts

Author: J.W. Langston

Publisher: IOS Press

Published: 2013-12-02

Total Pages: 264

ISBN-13: 1614993327

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In the summer of 1982, hospital emergency rooms in the San Francisco Bay Area were suddenly confronted with mysteriously “frozen” patients – young men and women who, though conscious, could neither move nor speak. Doctors were baffled, until neurologist J. William Langston, recognizing the symptoms of advanced Parkinson’s disease, administered L-dopa – the only known effective treatment – and “unfroze” his patient. Dr. Langston determined that this patient and five others had all used the same tainted batch of synthetic heroin, inadvertently laced with a toxin that had destroyed an area of their brains essential to normal movement. This same area, the substantia nigra, slowly deteriorates in Parkinson’s disease. As scientists raced to capitalize on this breakthrough, Dr. Langston struggled to salvage the lives of his frozen patients, for whom L-dopa provided only short-term relief. The solution he found lay in the most daring area of research: fetal-tissue transplants. The astonishing recovery of two of his patients garnered worldwide press coverage, helped overturn federal restrictions on fetal-tissue research, and offered hope to millions suffering from Parkinson’s, Alzheimer’s, and other degenerative brain disorders. This is the story behind the headline – a spellbinding account that brings to life the intellectual excitement, ethical dilemmas, and fierce competitiveness of medical research. This new updated edition of the classic neurological mystery tale, “The Case of the Frozen Addicts,” illuminates how the solution to a baffling mystery of the brain’s chemistry opened a new frontier in medicine and restored life to people without hope. “It begins with a series of quixotic discoveries, escalates to providing possible solutions for one of humanity’s most intractable medical problems, and then catapults the reader into the center of America’s hottest political arena – abortion and fetal sanctity. Bravo! A brilliant read.” – Laurie Garrett, author of The Coming Plague “[Langston and Palfreman] weave a highly readable and spellbinding medical detective tale... It is as absorbing as a good mystery, as entertaining as an exciting novel, and as enlightening as a good biography.” – Stanley Fahn, New England Journal of Medicine “I could not put it down... it is the lives of the ‘frozen addicts’ themselves – and the fullness with which this is presented – which makes the whole thing overwhelming.” – Oliver Sacks

Mitochondrial Dysfunction in Neurodegenerative Disorders
Mitochondrial Dysfunction in Neurodegenerative Disorders

Author: Amy Katherine Reeve

Publisher: Springer Science & Business Media

Published: 2011-11-15

Total Pages: 252

ISBN-13: 0857297015

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As age related diseases increase in prevalence and impact more significantly on medical resources it is imperative to understand these diseases and the mechanisms behind their progression. New research has stimulated a growing interest in mitochondrial involvement in neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease and multiple sclerosis and the mechanisms which lead from mitochondrial dysfunction to neurodegeneration. Mitochondrial Dysfunction in Neurodegenerative Disorders brings together contributions from leaders in the field internationally on the various ways in which mitochondrial dysfunction contributes to the pathogenesis of these diseases, guiding the reader through the basic functions of mitochondria and the mechanisms that lead to their dysfunction, to the consequences of this dysfunction on neuronal function before finishing with the modelling of these disorders and discussion of new potential therapeutic targets. Mitochondrial Dysfunction in Neurodegenerative Disorders provides an accessible, authoritative guide to this important area for neurologists; research and clinical neuroscientists; neuropathologists; and residents with an interest in clinical research.

Magnesium in the Central Nervous System
Magnesium in the Central Nervous System

Author: Robert Vink

Publisher: University of Adelaide Press

Published: 2011

Total Pages: 354

ISBN-13: 0987073052

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The brain is the most complex organ in our body. Indeed, it is perhaps the most complex structure we have ever encountered in nature. Both structurally and functionally, there are many peculiarities that differentiate the brain from all other organs. The brain is our connection to the world around us and by governing nervous system and higher function, any disturbance induces severe neurological and psychiatric disorders that can have a devastating effect on quality of life. Our understanding of the physiology and biochemistry of the brain has improved dramatically in the last two decades. In particular, the critical role of cations, including magnesium, has become evident, even if incompletely understood at a mechanistic level. The exact role and regulation of magnesium, in particular, remains elusive, largely because intracellular levels are so difficult to routinely quantify. Nonetheless, the importance of magnesium to normal central nervous system activity is self-evident given the complicated homeostatic mechanisms that maintain the concentration of this cation within strict limits essential for normal physiology and metabolism. There is also considerable accumulating evidence to suggest alterations to some brain functions in both normal and pathological conditions may be linked to alterations in local magnesium concentration. This book, containing chapters written by some of the foremost experts in the field of magnesium research, brings together the latest in experimental and clinical magnesium research as it relates to the central nervous system. It offers a complete and updated view of magnesiums involvement in central nervous system function and in so doing, brings together two main pillars of contemporary neuroscience research, namely providing an explanation for the molecular mechanisms involved in brain function, and emphasizing the connections between the molecular changes and behavior. It is the untiring efforts of those magnesium researchers who have dedicated their lives to unraveling the mysteries of magnesiums role in biological systems that has inspired the collation of this volume of work.

Integrative approach to Parkinson’s disease
Integrative approach to Parkinson’s disease

Author: Hi-Joon Park

Publisher: Frontiers Media SA

Published: 2020-01-30

Total Pages: 177

ISBN-13: 2889634094

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.

Neurodegenerative Diseases
Neurodegenerative Diseases

Author: Uday Kishore

Publisher: BoD – Books on Demand

Published: 2013-05-15

Total Pages: 642

ISBN-13: 9535110888

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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.