Nuclear Receptors License Phagocytosis In Mouse Models Of Alzheimer S Disease
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Nuclear Receptors License Phagocytosis In Mouse Models Of Alzheimer S Disease
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Author : Julie C Savage
language : en
Publisher:
Release Date : 2015
Nuclear Receptors License Phagocytosis In Mouse Models Of Alzheimer S Disease written by Julie C Savage and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015 with Alzheimer's disease categories.
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the deposition of extracellular fibrillar beta-amyloid (fAß) and accumulation of intraneuronal hyperphosphorylated tau. This pathology is accompanied by a robust inflammatory response mediated by the brain's resident immune cells, microglia, and macrophages derived from peripheral monocytes which invade the AD brain. These cells produce proinflammatory cytokines and reactive oxygen and nitrogen species, but cannot phagocytose and degrade fAß. Using nuclear receptor (NR) agonists, we demonstrate that it is possible to change the phenotype of microglia and macrophages in an AD environment and shift them to a pro-phagocytic state. NR agonists of LXR, PPAR¿, PPARd, and their obligate heterodimer partner RXR are able to induce expression of phagocytic TAM receptors MerTK and Axl in vitro. Furthermore, cultured cells respond to NR agonists and phagocytose more cargo in response to fAß and TAM ligands. Additionally, NR agonists rapidly increase MerTK and Axl levels in mouse models of AD, coincident with reduction of fAß. Microglia and macrophages in AD animals express high levels of MerTK and Axl on CD45+ plaque associated cells, and the levels of MerTK and Axl are increased further in animals treated with NR agonists. Bexarotene treatment also increases MerTK levels on TREM2+ and CD45hi cells as assayed by flow cytometry, lending data to support the hypothesis that MerTK+ plaque-associated cells are peripherally derived. Strikingly, bexarotene treatment of AD model mice reverses fAß induced phagocytic deficiency, as demonstrated with a slice-phagocytosis assay. We extend our studies to investigate the role of bexarotene on microglial and macrophage phenotype by utilizing a microarray study to investigate which genes are driven by bexarotene administration. Mononuclear phagocytes isolated from bexarotene treated animals display higher levels of proinflammatory and anti-inflammatory genes compared to vehicle treated controls. Interestingly, many genes involved in IL-1 signaling are differently expressed in bexarotene treated mice. Together our data demonstrate that NR agonists are capable of altering microglial phenotype to a more phagocytic state, thus allowing them to phagocytose Aß and facilitate its clearance. These data may provide a therapeutic strategy for the treatment of AD and other neurodegenerative diseases.
Current Thoughts On Dementia
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Author : Ghulam Md Ashraf
language : en
Publisher: Springer Nature
Release Date : 2022-07-06
Current Thoughts On Dementia written by Ghulam Md Ashraf and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-07-06 with Medical categories.
This informative book discusses the latest research on the risk factors and therapeutics in dementia. WHO calls dementia a public health priority. Dementia manifests as a group of symptoms associated with decline in memory or other thinking skills and is severe enough to reduce a person's ability to perform everyday activities. It occurs frequently among elderly people, but it is not necessarily part of the normal aging process. The book has been divided into two broad sections. The first section reviews the risk factors involved in developing dementia, including various medical conditions, lifestyle choices, as well as genetics. The latter section describes various therapeutic interventions in dementia. Although there is no known cure for dementia, this book underlines the current treatment strategies that could momentarily reduce the symptoms and improve the quality of life of the patients. This book highlights the global effort to find better ways to halt the progression of dementia and develop novel therapeutic strategies. The book would be an interesting read for advanced graduate students and researchers working in the field of neuroscience, genetics, and medicine. It will generate good interest to neurologists, psychiatrists, geriatricians, cardiologists, internal medicine practitioners, epidemiologist, and public health workers.
The M2 Macrophage
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Author : Tamás Röszer
language : en
Publisher: Springer Nature
Release Date : 2020-08-03
The M2 Macrophage written by Tamás Röszer and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-08-03 with Medical categories.
Macrophages are core components of the innate immune system. Once activated, they may have either pro- or anti-inflammatory effects that include pathogen killing, safe disposal of apoptotic cells or tissue renewal. The activation state of macrophages is conceptualized by the so-called M1/M2 model of polarization. M2 macrophages are not simply antagonists of M1 macrophages; rather, they represent a network of tissue resident macrophages with roles in tissue development and organ homeostasis. M2 macrophages govern functions at the interfaces of immunity, tissue development and turnover, metabolism, and endocrine signaling. Dysfunction in M2 macrophages can ruin the healthy interplay between the immune system and metabolic processes, and lead to diseases such as insulin resistance, metabolic syndrome, and type 1 and 2 diabetes mellitus. Furthermore, M2 macrophages are essential for healthy tissue development and immunological self-tolerance. Worryingly, these functions of M2 macrophages can also be disrupted, resulting in tumor growth and autoimmunity. This book comprehensively discusses the biology of M2 macrophages, summarizes the current state of knowledge, and highlights key questions that remain unanswered.
Neuroprotection
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Author : Matilde Otero-Losada
language : en
Publisher: BoD – Books on Demand
Release Date : 2020-11-26
Neuroprotection written by Matilde Otero-Losada and has been published by BoD – Books on Demand this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-11-26 with Medical categories.
Neurological disease affects nearly 25%–30% of the world’s population, exerting enormous financial strain on the healthcare system. Estimated current costs are around $800 annual billion, and this number is expected to increase exponentially as the global population ages. As such, new and alternative neuroprotective strategies are urgently needed. This book examines some of the most promising approaches in neuroprotection as well as discusses current goals and prospects. Organized into three sections, chapters cover such topics as the use of cannabinoids, medicinal plants, and essential oils in Alzheimer’s and Parkinson’s; protein misfolding and the neuroprotective potential of vitamin E in cerebral ischemia; and potential new neurological treatments and their mechanisms of action.
Purinergic Signaling In Health And Disease
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Author : Eric Boué-Grabot
language : en
Publisher: Frontiers Media SA
Release Date : 2020-03-13
Purinergic Signaling In Health And Disease written by Eric Boué-Grabot and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-03-13 with categories.
Synaptic Loss And Neurodegeneration
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Author : Marie-Ève Tremblay
language : en
Publisher: Frontiers Media SA
Release Date : 2021-06-16
Synaptic Loss And Neurodegeneration written by Marie-Ève Tremblay and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021-06-16 with Science categories.
Cell Cell Interactions Controlling Neuronal Functionality In Health And Disease
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Author : Stefano Angiari
language : en
Publisher: Frontiers Media SA
Release Date : 2022-07-27
Cell Cell Interactions Controlling Neuronal Functionality In Health And Disease written by Stefano Angiari and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-07-27 with Science categories.
Alzheimer S Disease From Basic Research To Clinical Applications
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Author : Hermann J. Gertz
language : en
Publisher: Springer Science & Business Media
Release Date : 2013-06-29
Alzheimer S Disease From Basic Research To Clinical Applications written by Hermann J. Gertz and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-06-29 with Medical categories.
As human longevity continues to be extended, so will the impact of age-associated dementia on individual lives and society. Alzheimer’s disease as the most common cause of dementia in the elderly remains a sentinal problem and its underlying pathology is still poorly understood. Available therapeutic strategies require considerable refinement and the development of new therapeutic strategies need input from basic research. Thus continued efforts are necessary both to understand basic mechanisms of the condition and to achieve more powerfull therapies. This volume brings together the reports of basic scientists and clinical investigators. The chapters provide a spectrum of information valuable for clinicians and scientists. This issue bridges the gap between laboratory work in basic science and the development of urgently needed therapeutic strategies. Areas presented are the molecular and cellular biology of the disease, pathogenetic mechanisms and potential therapeutic targets, genetics, risk factors, strategies of prevention and treatment as well as practical aspects of medical and social care for patients with Alzheimer’s disease.
Molecular Neurology
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Author : Stephen Waxman
language : en
Publisher: Elsevier
Release Date : 2010-07-26
Molecular Neurology written by Stephen Waxman and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010-07-26 with Medical categories.
Why a book on molecular neurology? Molecular neuroscience is advancing at a spectacular rate. As it does so, it is revealing important clues to the pathogenesis and pathophysiology of neurological diseases, and to the therapeutic targets that they present. Medicines work by targeting molecules. The more specific the targeting, the more specific the actions, and the fewer the side effects. Molecular Neurology highlights, for graduate and MD-PhD students, research fellows and research-oriented clinical fellows, and researchers in the neurosciences and other biomedical sciences, the principles underlying molecular medicine as related to neurology. Written by internationally recognized experts, this well-illustrated and well-referenced book presents the most up-to-date principles and disease examples relevant to molecular neurology, and reviews the concepts, strategies, and latest progress in this field. This book will interest anyone studying the molecular basis of neurology, or developing new therapies in neurology. Describes the newest molecular aspects of neurological disorders Provides an introduction to neurological disorders for basic scientists Updates clinicians and clinical researchers on the most recent developments
Encyclopedia Of Signaling Molecules
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Author : Sangdun Choi
language : en
Publisher: Springer
Release Date : 2017-12-15
Encyclopedia Of Signaling Molecules written by Sangdun Choi and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-12-15 with Medical categories.
The second edition of this encyclopedia presents over 400 biologically important signaling molecules and the content is built on the core concepts of their functions along with early findings written by some of the world’s foremost experts. The molecules are described by recognized leaders in each molecule. The interactions of these single molecules in signal transduction networks will also be explored. This encyclopedia marks a new era in overview of current cellular signaling molecules for the specialist and the interested non-specialist alike. Currently, there are more than 30,000 genes in human genome. However, not all the proteins encoded by these genes work equally in order to maintain homeostasis. Understanding the important signaling molecules as completely as possible will significantly improve our research-based teaching and scientific capabilities.