Intracellular Cholesterol Trafficking

Intracellular Cholesterol Trafficking
Author: T.Y. Chang
Publisher: Springer Science & Business Media
Total Pages: 298
Release: 2012-12-06
Genre: Science
ISBN: 1461551137

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INTRODUCTION AND RATIONALE FOR INTRACELLULAR CHOLESTEROL TRAFFICKING This volume is an elaboration of an earlier small meeting held in St. Louis, Missouri. In April 1997, many of the authors met for a two-day meeting devoted entirely to intracellular cholesterol trafficking. The rationale for this meeting was that investigators interested in this topic worked in a variety of fields, and rarely, if ever, all met together. Everybody knew each other's papers but mostly worked in isolation from one another. Understanding of cholesterol trafficking also appeared to have reached the point where it would start to rapidly expand beyond these few laboratories. Understanding of cholesterol trafficking was moving from a largely descriptive science into the molecular age. It seemed a good time to get together and see how much we agreed upon up to this point. More authors contributed to this volume than attended the St. Louis meeting. That meeting was generously funded by grants from Bristol-Myers Squibb, Merck and Company and Parke-Davis, however, the total funding available limited the size of the meeting. For the book, we are not so limited and have tried to be as inclusive as possible and pretty much invited everyone who is presently active in this area. We were quite fortunate to successfully recruit the authors we sought for each of these chapters. The authors and their contributions can be organized by particular interests and particular areas of expertise.

NPC1-mediated Lysosomal Cholesterol Efflux Tunes Ca2+ Signaling and Plasticity

NPC1-mediated Lysosomal Cholesterol Efflux Tunes Ca2+ Signaling and Plasticity
Author: Scott Tiscione
Publisher:
Total Pages:
Release: 2020
Genre:
ISBN:

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Niemann-Pick Type C1 (NPC1) protein is essential for the transport of externally-derived cholesterol from lysosomes to other organelles. Deficiency of NPC1 underlies the progressive Niemann-Pick Type C1 neurodegenerative disorder. Currently, there are no curative therapies for this fatal disease and the mechanisms by why which these mutations result in neuronal cell death are not fully understood. We have observed that downstream of the NPC1-dependent perturbation of cholesterol homeostasis are extensive changes to cellular Ca2+ dynamics. Moreover, many neurodegenerative diseases share a correlation between impaired cholesterol homeostasis and altered Ca2+ signaling, including Alzheimer's, Parkinson's, and Huntington's disease. Despite these correlations, the precise molecular mechanisms that link dysfunction in cholesterol metabolism and Ca2+ signaling to neuropathology are poorly understood. Given the Ca2+ hypothesis of neurodegeneration, which posits that altered Ca2+ signaling and homeostasis contributes to neuropathology, we investigated the mechanism by which NPC1-mediated lysosomal cholesterol efflux alters Ca2+ dynamics and the cellular consequences when the pathway is perturbed. Herein, we describe a novel pathway through which NPC1-mediated cholesterol efflux regulates and tunes cellular Ca2+ signaling and handling in a sterol-response element binding protein (SREBP) and Presenilin 1 (PS1) dependent manner. Targeting either the SREBP pathway or PS1 protein rescues the Ca2+ phenotypes of NPC1 disease and the downstream cellular consequences including lysosomal dysfunction and altered synaptic plasticity. Our results further our understanding of this complex signaling pathway in both health and disease and reveal a promising therapeutic target in neurodegenerative diseases of impaired cholesterol and Ca2+ homeostasis.

Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease

Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease
Author: Roger N. Rosenberg
Publisher: Elsevier
Total Pages: 1465
Release: 2014-10-28
Genre: Science
ISBN: 0124105491

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Rosenberg’s Molecular and Genetic Basis of Neurologic and Psychiatric Disease, Fifth Edition provides a comprehensive introduction and reference to the foundations and key practical aspects relevant to the majority of neurologic and psychiatric disease. A favorite of over three generations of students, clinicians and scholars, this new edition retains and expands the informative, concise and critical tone of the first edition. This is an essential reference for general medical practitioners, neurologists, psychiatrists, geneticists, and related professionals, and for the neuroscience and neurology research community. The content covers all aspects essential to the practice of neurogenetics to inform clinical diagnosis, treatment and genetic counseling. Every chapter has been thoroughly revised or newly commissioned to reflect the latest scientific and medical advances by an international team of leading scientists and clinicians. The contents have been expanded to include disorders for which a genetic basis has been recently identified, together with abundant original illustrations that convey and clarify the key points of the text in an attractive, didactic format. Previous editions have established this book as the leading tutorial reference on neurogenetics. Researchers will find great value in the coverage of genomics, animal models and diagnostic methods along with a better understanding of the clinical implications. Clinicians will rely on the coverage of the basic science of neurogenetics and the methods for evaluating patients with biochemical abnormalities or gene mutations, including links to genetic testing for specific diseases. Comprehensive coverage of the neurogenetic foundation of neurological and psychiatric disease Detailed introduction to both clinical and basic research implications of molecular and genetic understanding of the brain Detailed coverage of genomics, animal models and diagnostic methods with new coverage of evaluating patients with biochemical abnormalities or gene mutations

Organelle Contact Sites

Organelle Contact Sites
Author: Mitsuo Tagaya
Publisher: Springer
Total Pages: 254
Release: 2017-08-16
Genre: Science
ISBN: 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.

Therapeutic Oligonucleotides

Therapeutic Oligonucleotides
Author: Jens Kurreck
Publisher: Royal Society of Chemistry
Total Pages: 362
Release: 2008
Genre: Medical
ISBN: 0854041168

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This book provides a compelling overall update on current status of RNA interference

Cyclodextrin

Cyclodextrin
Author: Poonam Arora
Publisher: BoD – Books on Demand
Total Pages: 334
Release: 2018-04-18
Genre: Science
ISBN: 1789230683

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The book is devoted to the highly versatile and potential ingredient Cyclodextrin, a family of cyclic oligosaccharides composed of ?-(1,4)-linked glucopyranose subunits. Its molecular complexation phenomena and negligible cytotoxic effects attribute toward its application such as in pharmaceuticals, cosmetics, food, agriculture, textile, separation process, analytical methods, catalysis, environment protection, and diagnostics. Efforts have also been made to concentrate on recent research outcomes along with future prospects of cyclodextrins to attract the interest of scientists from the industry and academia. The contributions of the authors are greatly acknowledged, without which this compilation would not have been possible.