Nuclear Receptors As Therapeutic Targets For Alzheimer S Disease
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Nuclear Receptors As Therapeutic Targets For Alzheimer S Disease
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Author : Rebecca Courtney
language : en
Publisher:
Release Date : 2017
Nuclear Receptors As Therapeutic Targets For Alzheimer S Disease written by Rebecca Courtney and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017 with Alzheimer's disease categories.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid beta (Aß) species in the brain. This is followed by robust neuroinflammation, the development of neurofibrillary tangles composed of tau, synaptic dysfunction, neuronal death, and the progressive development of cognitive and behavioral impairments. We demonstrate that nuclear receptors make useful therapeutic targets to address several aspects of this pathology. Using agonists for PPAR¿ and LXR, we show that a short-term treatment of 9 days is sufficient to ameliorate behavioral impairments, attenuate neuroinflammation, and induce partial clearance of Aß from the brain in an AD mouse model. This combination therapy acted on astrocytes to increase the expression and lipidation of apoE, and on microglia to increase their rate of Aß degradation and ability to associate with Aß plaques. We also demonstrate that some nuclear receptors, such as Nurr1, are valuable targets for addressing the neuronal pathology associated with AD. Knocking down Nurr111decreased the survival of vulnerable neurons in an AD mouse model. Conversely, increasing Nurr1 expression increased neuronal survival, decreased dystrophic neurites, and ameliorated local Aß pathology including decreasing intraneuronal Aß by about 30%. Together, these data demonstrate that drugs targeting multiple nuclear receptors can be valuable to treat various aspects of AD pathology. Interestingly, LXR, PPAR¿, and Nurr1 can all be activated by the RXR agonist bexarotene. These data provide insight into the mechanisms by which bexarotene might act, and suggest several novel therapeutic approaches to the treatment of AD.
Therapeutic Targets
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Author : Luis M. Botana
language : en
Publisher: John Wiley & Sons
Release Date : 2012-04-20
Therapeutic Targets written by Luis M. Botana and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-04-20 with Medical categories.
The Latest Applications For Cellmechanism Research in Drug Discovery Designed to connect research on cell mechanisms with the drug discovery process, Therapeutic Targets: Modulation, Inhibition, and Activation introduces readers to a range of new concepts and novel approaches to drug screening and therapeutic drug targeting to help inform future avenues of drug research. Highly topical, this accessible edited volume features chapters contributed by respected experts from around the globe. The book helps postgraduate students and professional scientists working in academia and industry understand the molecular mechanisms of pharmacology, current pharmacological knowledge, and future perspectives in drug discovery, focusing on important biochemical protein targets and drug targeting strategies for specific diseases. Examining the pharmacology of therapeutically undefined targets and their potential applications, it includes chapters on traditional therapeutic targets, including enzymes (phosphodiesterases and proteases), ion channels, and G protein-coupled receptors, as well as more recently identified avenues of exploration, such as lipids, nuclear receptors, gene promoters, and more. Since different diseases require different targeting techniques, the book also includes dedicated chapters on strategies for investigating Alzheimer's, diabetes, pain, and inflammation treatments. Concluding with a cross-sectional look at new approaches in drug screening, Therapeutic Targets is an invaluable resource for understanding where the next generation of drugs are likely to emerge.
Nuclear Receptors As Molecular Targets For Cardiometabolic And Central Nervous System Diseases
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Author : J.L. Junien
language : en
Publisher: IOS Press
Release Date : 2008-07-16
Nuclear Receptors As Molecular Targets For Cardiometabolic And Central Nervous System Diseases written by J.L. Junien and has been published by IOS Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-07-16 with Medical categories.
Nuclear receptors are a family of transcription factors consisting of 49 members identified in the human genome. Nuclear receptors regulate transcription by binding to response elements in the regulatory regions of target genes and thereby affect expression of genes involved in differentiation, growth, lipid homeostasis, inflammation and immunity. Over the past two decades significant advances have been made in the understanding of the regulation of gene expression by nuclear receptors. The knowledge on nuclear receptors has delivered novel therapies for lipid control and hormone replacement, and for management of cancer and diabetes. Therefore, nuclear receptors are attractive molecular targets for design of therapy for diabetes, obesity, atherosclerosis, cancer, inflammation and neurodegeneration. The focus of this volume is centered on the mechanistic involvement of nuclear receptors in cardiological, metabolic and neurological disorders, on possible explanation of pathways involved in pathogenesis, on susceptibility to and prevention of metabolic and neurological disorders and on the aspects of drug finding including chemistry and rational drug design. This volume reviews recent progress on nuclear receptors critically and will intrigue those pursuing interest in physiology, pathology and medicine.
Purinergic Receptors As Potential Therapeutic Targets In Alzheimer S Disease
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Author :
language : en
Publisher:
Release Date : 2016
Purinergic Receptors As Potential Therapeutic Targets In Alzheimer S Disease written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016 with categories.
Deciphering Drug Targets For Alzheimer S Disease
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Author : Dileep Kumar
language : en
Publisher: Springer Nature
Release Date : 2023-10-02
Deciphering Drug Targets For Alzheimer S Disease written by Dileep Kumar and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2023-10-02 with Medical categories.
This book explains the fundamental characteristics and biofunctionality of Alzheimer’s Disease drug targets and provides up-to-date information on the full range of their biomedical applications. An introductory section gives an overview of the recent developments related to drug targets identified and studied related to Alzheimer’s Disease and key developments from preclinical and clinical studies focusing on various molecular targets related to AD and dementia by subject experts all around the globe. Here, individual chapters address the progress and perspectives in human and non-human research, role of various biomarkers as an overview, advanced gene therapy, and novel compounds for therapeutic targets for Alzheimer’s disease. The book will be essential reading for graduate students, scientists, and engineers in any of the biomedical research fields in which efforts are being made to utilize novel drug targets and develop effective strategies for new drug targeting and delivery in Alzheimer’s disease treatment.
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.
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.
Nuclear Receptors As Drug Targets
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Author : Eckhard Ottow
language : en
Publisher: John Wiley & Sons
Release Date : 2008-09-08
Nuclear Receptors As Drug Targets written by Eckhard Ottow and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-09-08 with Medical categories.
Edited by two experts working at the pioneering pharmaceutical company and major global player in hormone-derived drugs, this handbook and reference systematically treats the drug development aspects of all human nuclear receptors, including recently characterized receptors such as PPAR, FXR and LXR. Authors from leading pharmaceutical companies around the world present examples and real-life data from their own work.
Biophysical Techniques In Drug Discovery
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Author : Angeles Canales
language : en
Publisher: Royal Society of Chemistry
Release Date : 2017-11-14
Biophysical Techniques In Drug Discovery written by Angeles Canales and has been published by Royal Society of Chemistry this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-11-14 with Science categories.
Biophysical techniques are used in many key stages of the drug discovery process including in screening for new receptor ligands, in characterising drug mechanisms, and in validating data from biochemical and cellular assays. This book provides an overview of the biophysical methods applied in drug discovery today, including traditional techniques and newer developments. Perspectives from academia and industry across a spectrum of techniques are brought together in a single volume. Small and biotherapeutic approaches are covered and strengths and limitations of each technique are presented. Case studies illustrate the application of each technique in real applied examples. Finally, the book covers recent developments in areas such as electron microscopy with discussions of their possible impact on future drug discovery. This is a go-to volume for biophysicists, analytical chemists and medicinal chemists providing a broad overview of techniques of contemporary interest in drug discovery.
Alzheimer Disease New Insights For The Healthcare Professional 2012 Edition
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Author :
language : en
Publisher: ScholarlyEditions
Release Date : 2012-12-10
Alzheimer Disease New Insights For The Healthcare Professional 2012 Edition written by and has been published by ScholarlyEditions this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-10 with Medical categories.
Alzheimer Disease: New Insights for the Healthcare Professional / 2012 Edition is a ScholarlyEditions™ eBook that delivers timely, authoritative, and comprehensive information about Alzheimer Disease. The editors have built Alzheimer Disease: New Insights for the Healthcare Professional / 2012 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Alzheimer Disease in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Alzheimer Disease: New Insights for the Healthcare Professional / 2012 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.