Protein Misfolding And Proteostasis Impairment In Aging And Neurodegeneration From Spreading Studies To Therapeutic Approaches

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Protein Misfolding and Proteostasis Impairment in Aging and Neurodegeneration: From Spreading Studies to Therapeutic Approaches

Author : Claudia Duran-Aniotz
Publisher : Frontiers Media SA
ISBN 13 : 2889746070
Total Pages : 265 pages
Book Rating : 4.8/5 (897 download)

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Book Synopsis Protein Misfolding and Proteostasis Impairment in Aging and Neurodegeneration: From Spreading Studies to Therapeutic Approaches by : Claudia Duran-Aniotz

Download or read book Protein Misfolding and Proteostasis Impairment in Aging and Neurodegeneration: From Spreading Studies to Therapeutic Approaches written by Claudia Duran-Aniotz and published by Frontiers Media SA. This book was released on 2022-10-05 with total page 265 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Proteostasis and Disease

Author : Rosa Barrio
Publisher : Springer Nature
ISBN 13 : 3030382664
Total Pages : 350 pages
Book Rating : 4.0/5 (33 download)

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Book Synopsis Proteostasis and Disease by : Rosa Barrio

Download or read book Proteostasis and Disease written by Rosa Barrio and published by Springer Nature. This book was released on 2020-04-09 with total page 350 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book, written by members of the European network PROTEOSTASIS, provides an up-to-date review of the research regarding protein homeostasis in health and disease. With new discoveries contributing to the increasing complexity of this topic, the book offers a detailed overview of the pathways regulating protein homeostasis, including autophagy and the ubiquitin protein family. Following a basic introduction, it explains how defects in protein homeostasis contribute to numerous pathologies, including cancer, neurodegeneration, inflammation and a number of rare diseases. In addition, it discusses, the role of protein homeostasis in cellular development and physiology. Highlighting the latest research in the field of protein homeostasis and its implications for various clinically relevant diseases, the book appeals to researchers and clinicians, while also offering a reference guide for scholars who are new to the field.

The Molecular and Cellular Basis of Neurodegenerative Diseases

Author : Michael S. Wolfe
Publisher : Academic Press
ISBN 13 : 0128113057
Total Pages : 560 pages
Book Rating : 4.1/5 (281 download)

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Book Synopsis The Molecular and Cellular Basis of Neurodegenerative Diseases by : Michael S. Wolfe

Download or read book The Molecular and Cellular Basis of Neurodegenerative Diseases written by Michael S. Wolfe and published by Academic Press. This book was released on 2018-03-29 with total page 560 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Molecular and Cellular Basis of Neurodegenerative Diseases: Underlying Mechanisms presents the pathology, genetics, biochemistry and cell biology of the major human neurodegenerative diseases, including Alzheimer’s, Parkinson’s, frontotemporal dementia, ALS, Huntington’s, and prion diseases. Edited and authored by internationally recognized leaders in the field, the book's chapters explore their pathogenic commonalities and differences, also including discussions of animal models and prospects for therapeutics. Diseases are presented first, with common mechanisms later. Individual chapters discuss each major neurodegenerative disease, integrating this information to offer multiple molecular and cellular mechanisms that diseases may have in common. This book provides readers with a timely update on this rapidly advancing area of investigation, presenting an invaluable resource for researchers in the field. Covers the spectrum of neurodegenerative diseases and their complex genetic, pathological, biochemical and cellular features Focuses on leading hypotheses regarding the biochemical and cellular dysfunctions that cause neurodegeneration Details features, advantages and limitations of animal models, as well as prospects for therapeutic development Authored by internationally recognized leaders in the field Includes illustrations that help clarify and consolidate complex concepts

Nature's Robots

Author : Charles Tanford
Publisher : OUP Oxford
ISBN 13 : 0191578517
Total Pages : 312 pages
Book Rating : 4.1/5 (915 download)

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Book Synopsis Nature's Robots by : Charles Tanford

Download or read book Nature's Robots written by Charles Tanford and published by OUP Oxford. This book was released on 2003-11-27 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proteins are amazingly versatile molecules. They make the chemical reactions happen that form the basis for life, they transmit signals in the body, they identify and kill foreign invaders, they form the engines that make us move, and they record visual images. All of this is now common knowledge, but it was not so a hundred years ago. Nature's Robots is an authoritative history of protein science, from the origins of protein research in the nineteenth century, when the chemical constitution of 'protein' was first studied and heatedly debated and when there was as yet no glimmer of the functional potential of substances in the 'protein' category, to the determination of the first structures of individual proteins at atomic resolution - when positions of individual atoms were first specified exactly and bonding between neighbouring atoms precisely defined. Tanford and Reynolds, who themselves made major contributions to the golden age of protein science, have written a remarkably vivid account of this history. It is a fascinating story, involving heroes from the past, working mostly alone or in small groups, usually with little support from formal research groups. It is also a story that embraces a number of historically important scientific controversies. Written in clear and accessible prose, Nature's Robots will appeal to general readers with an interest in popular science, in addition to professional scientists and historians of science.

Natural Products and Neuroprotection

Author : Cristina Angeloni
Publisher : MDPI
ISBN 13 : 303936216X
Total Pages : 338 pages
Book Rating : 4.0/5 (393 download)

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Book Synopsis Natural Products and Neuroprotection by : Cristina Angeloni

Download or read book Natural Products and Neuroprotection written by Cristina Angeloni and published by MDPI. This book was released on 2020-06-17 with total page 338 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neurodegenerative diseases, including Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis, are the most common pathologies of the central nervous system currently without a cure. They share common molecular and cellular characteristics, including protein misfolding, mitochondrial dysfunction, glutamate toxicity, dysregulation of calcium homeostasis, oxidative stress, inflammation, and ageing, which contribute to neuronal death. Efforts to treat these diseases are often limited by their multifactorial etiology. Natural products, thanks to their multitarget activities, are considered promising alternatives for the treatment of neurodegeneration. This book deals with two different forms of natural products: extracts and isolated compounds. The study of the bioactivity of the extracts is extremely important as many studies have demonstrated the synergistic effect of the combination of different natural products. On the other hand, the investigation of the activity of specifically isolated natural products can be also important to understand their cellular and molecular mechanisms and to define the specific bioactive components in extracts or foods. This book can be considered an important contribution to knowledge of the neuroprotective effect of natural products and presents a great deal of information, related to both the benefits but also the limitations of their use in counteracting neurodegeneration.

Tau oligomers

Author : Jesus Avila
Publisher : Frontiers E-books
ISBN 13 : 288919261X
Total Pages : 114 pages
Book Rating : 4.8/5 (891 download)

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Book Synopsis Tau oligomers by : Jesus Avila

Download or read book Tau oligomers written by Jesus Avila and published by Frontiers E-books. This book was released on 2014-08-18 with total page 114 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neurofibrillary tangles (NFTs) composed of intracellular aggregates of tau protein are a key neuropathological feature of Alzheimer’s Disease (AD) and other neurodegenerative diseases, collectively termed tauopathies. The abundance of NFTs has been reported to correlate positively with the severity of cognitive impairment in AD. However, accumulating evidences derived from studies of experimental models have identified that NFTs themselves may not be neurotoxic. Now, many of tau researchers are seeking a “toxic” form of tau protein. Moreover, it was suggested that a “toxic” tau was capable to seed aggregation of native tau protein and to propagate in a prion-like manner. However, the exact neurotoxic tau species remain unclear. Because mature tangles seem to be non-toxic component, “tau oligomers” as the candidate of “toxic” tau have been investigated for more than one decade. In this topic, we will discuss our consensus of “tau oligomers” because the term of “tau oligomers” [e.g. dimer (disulfide bond-dependent or independent), multimer (more than dimer), granular (definition by EM or AFM) and maybe small filamentous aggregates] has been used by each researchers definition. From a biochemical point of view, tau protein has several unique characteristics such as natively unfolded conformation, thermo-stability, acid-stability, and capability of post-translational modifications. Although tau protein research has been continued for a long time, we are still missing the mechanisms of NFT formation. It is unclear how the conversion is occurred from natively unfolded protein to abnormally mis-folded protein. It remains unknown how tau protein can be formed filaments [e.g. paired helical filament (PHF), straight filament and twisted filament] in cells albeit in vitro studies confirmed tau self-assembly by several inducing factors. Researchers are still debating whether tau oligomerization is primary event rather than tau phosphorylation in the tau pathogenesis. Inhibition of either tau phosphorylation or aggregation has been investigated for the prevention of tauopathies, however, it will make an irrelevant result if we don’t know an exact target of neurotoxicity. It is a time to have a consensus of definition, terminology and methodology for the identification of “tau oligomers”.

Molecular Mechanisms of Neurodegenerative Diseases

Author : Marie-Francoise Chesselet
Publisher : Springer Science & Business Media
ISBN 13 : 1592590063
Total Pages : 416 pages
Book Rating : 4.5/5 (925 download)

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Book Synopsis Molecular Mechanisms of Neurodegenerative Diseases by : Marie-Francoise Chesselet

Download or read book Molecular Mechanisms of Neurodegenerative Diseases written by Marie-Francoise Chesselet and published by Springer Science & Business Media. This book was released on 2000-10-19 with total page 416 pages. Available in PDF, EPUB and Kindle. Book excerpt: With the unprecedented identification of new mutation mechanisms in neurodegenerative diseases and the emergence of common mechanisms among diseases that were once considered unrelated, neurobiologists are poised for the development of new therapies based on high throughput screenings and a better understanding of the molecular and cellular mechanisms leading to neurodegeneration. In Molecular Mechanisms of Neurodegenerative Diseases, Marie-Francoise Chesselet, MD, PhD, and a panel of leading researchers and neurologists from industry and academia critically review the most recent advances from different yet complementary points of view. Focusing on Alzheimer's, Parkinson's, and CAG triplet repeat diseases, the authors show how studies of cellular and genetically engineered animal models have enhanced our understanding of the molecular mechanisms of neurodegenerative diseases and may lead to the development of new therapeutics. Topics include the role of Ab toxicity, glial cells, and inflammation in Alzheimer's disease; the formation of abnormal protein fragments across several diseases, the impact of dopamine and mitochondrial dysfunction on neurodegeneration; and the potential of genetics to identify the molecular mechanisms of neurodegenerative diseases. Authoritative and insightful, Molecular Mechanisms of Neurodegenerative Diseases synthesizes the novel ideas and concepts now emerging to create a fresh understanding of neurodegenerative disorders, one that promises to lead to powerful new therapies that prevent, delay the onset, slow the progression, or even cure these cruel diseases.

Imaging in Neurodegenerative Disorders

Author : Luca Saba
Publisher : Oxford University Press, USA
ISBN 13 : 0199671613
Total Pages : 585 pages
Book Rating : 4.1/5 (996 download)

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Book Synopsis Imaging in Neurodegenerative Disorders by : Luca Saba

Download or read book Imaging in Neurodegenerative Disorders written by Luca Saba and published by Oxford University Press, USA. This book was released on 2015 with total page 585 pages. Available in PDF, EPUB and Kindle. Book excerpt: This text summarizes the latest developments in imaging techniques and other new diagnostic methods as applied to the neurodegenerative disorders.

Proteopathic Seeds and Neurodegenerative Diseases

Author : Mathias Jucker
Publisher : Springer Science & Business Media
ISBN 13 : 3642354912
Total Pages : 163 pages
Book Rating : 4.6/5 (423 download)

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Book Synopsis Proteopathic Seeds and Neurodegenerative Diseases by : Mathias Jucker

Download or read book Proteopathic Seeds and Neurodegenerative Diseases written by Mathias Jucker and published by Springer Science & Business Media. This book was released on 2013-03-27 with total page 163 pages. Available in PDF, EPUB and Kindle. Book excerpt: The misfolding and aggregation of specific proteins is an early and obligatory event in many of the age-related neurodegenerative diseases of humans. The initial cause of this pathogenic cascade and the means whereby disease spreads through the nervous system, remain uncertain. A recent surge of research, first instigated by pathologic similarities between prion disease and Alzheimer’s disease, increasingly implicates the conversion of disease-specific proteins into an aggregate-prone b-sheet-rich state as the prime mover of the neurodegenerative process. This prion-like corruptive protein templating or seeding now characterizes such clinically and etiologically diverse neurological disorders as Alzheimer ́s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and frontotemporal lobar degeneration. Understanding the misfolding, aggregation, trafficking and pathogenicity of the affected proteins could therefore reveal universal pathomechanistic principles for some of the most devastating and intractable human brain disorders. It is time to accept that the prion concept is no longer confined to prionoses but is a promising concept for the understanding and treatment of a remarkable variety of diseases that afflict primarily our aging society.

Cyclin Dependent Kinase 5 (Cdk5)

Author : Nancy Y. Ip
Publisher : Springer Science & Business Media
ISBN 13 : 0387788875
Total Pages : 326 pages
Book Rating : 4.3/5 (877 download)

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Book Synopsis Cyclin Dependent Kinase 5 (Cdk5) by : Nancy Y. Ip

Download or read book Cyclin Dependent Kinase 5 (Cdk5) written by Nancy Y. Ip and published by Springer Science & Business Media. This book was released on 2009-02-28 with total page 326 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cyclin Dependent Kinase 5 provides a comprehensive and up-to-date collection of reviews on the discovery, signaling mechanisms and functions of Cdk5, as well as the potential implication of Cdk5 in the treatment of neurodegenerative diseases. Since the identification of this unique member of the Cdk family, Cdk5 has emerged as one of the most important signal transduction mediators in the development, maintenance and fine-tuning of neuronal functions and networking. Further studies have revealed that Cdk5 is also associated with the regulation of neuronal survival during both developmental stages and in neurodegenerative diseases. These observations indicate that precise control of Cdk5 is essential for the regulation of neuronal survival. The pivotal role Cdk5 appears to play in both the regulation of neuronal survival and synaptic functions thus raises the interesting possibility that Cdk5 inhibitors may serve as therapeutic treatment for a number of neurodegenerative diseases.

Brain Transcriptome

Author :
Publisher : Academic Press
ISBN 13 : 0128013192
Total Pages : 365 pages
Book Rating : 4.1/5 (28 download)

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Book Synopsis Brain Transcriptome by :

Download or read book Brain Transcriptome written by and published by Academic Press. This book was released on 2014-08-27 with total page 365 pages. Available in PDF, EPUB and Kindle. Book excerpt: Published since 1959, International Review of Neurobiology is a well-known series appealing to neuroscientists, clinicians, psychologists, physiologists, and pharmacologists. Led by an internationally renowned editorial board, this important serial publishes both eclectic volumes made up of timely reviews and thematic volumes that focus on recent progress in a specific area of neurobiology research. This volume, concentrates on the brain transcriptome. Brings together cutting-edge research on the brain transcriptome

Apolipoprotein E and Alzheimer’s Disease

Author : A.D. Roses
Publisher : Springer Science & Business Media
ISBN 13 : 3642801099
Total Pages : 208 pages
Book Rating : 4.6/5 (428 download)

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Book Synopsis Apolipoprotein E and Alzheimer’s Disease by : A.D. Roses

Download or read book Apolipoprotein E and Alzheimer’s Disease written by A.D. Roses and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 208 pages. Available in PDF, EPUB and Kindle. Book excerpt: There is now considerable genetic evidence that the type 4 allele of the apolipoprotein E gene is a major susceptibility factor associated with late-onset Alzheimer's disease, the common form of the disease defined as starting after sixty years of age. The role of apolipoprotein E in normal brain metabolism and in the pathogenesis of Alzheimer's disease are new and exciting avenues of research. This book, written by the most outstanding scientists in this new filed, is the first presentation of results concerning the implications of apolipoprotein E on the genetics, cell biology, neuropathology, biochemistry, and therapeutic management of Alzheimer's disease.

Homeostatic Control of Brain Function

Author : Detlev Boison
Publisher : Oxford University Press
ISBN 13 : 0199322295
Total Pages : 657 pages
Book Rating : 4.1/5 (993 download)

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Book Synopsis Homeostatic Control of Brain Function by : Detlev Boison

Download or read book Homeostatic Control of Brain Function written by Detlev Boison and published by Oxford University Press. This book was released on 2016 with total page 657 pages. Available in PDF, EPUB and Kindle. Book excerpt: Homeostatic Control of Brain Function offers a broad view of brain health and diverse perspectives for potential treatments, targeting key areas such as mitochondria, the immune system, epigenetic changes, and regulatory molecules such as ions, neuropeptides, and neuromodulators. Loss of homeostasis becomes expressed as a diverse array of neurological disorders. Each disorder has multiple comorbidities - with some crossing over several conditions - and often disease-specific treatments remain elusive. When current pharmacological therapies result in ineffective and inadequate outcomes, therapies to restore and maintain homeostatic functions can help improve brain health, no matter the diagnosis. Employing homeostatic therapies may lead to future cures or treatments that address multiple comorbidities. In an age where brain diseases such as Alzheimer's or Parkinson's are ever present, the incorporation of homeostatic techniques could successfully promote better overall brain health. Key Features include · A focus on the homeostatic controls that significantly depend on the way one lives, eats, and drinks. · Highlights from emerging research in non-pharmaceutical therapies including botanical medications, meditation, diet, and exercise. · Incorporation of homeostatic therapies into existing basic and clinical research paradigms. · Extensive scientific basic and clinical research ranging from molecules to disorders. · Emerging practical information for improving homeostasis. · Examples of homeostatic therapies in preventing and delaying dysfunction. Both editors, Detlev Boison and Susan Masino, bring their unique expertise in homeostatic research to the overall scope of this work. This book is accessible to all with an interest in brain health; scientist, clinician, student, and lay reader alike.

The Big Book on Small Heat Shock Proteins

Author : Robert M. Tanguay
Publisher : Springer
ISBN 13 : 331916077X
Total Pages : 610 pages
Book Rating : 4.3/5 (191 download)

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Book Synopsis The Big Book on Small Heat Shock Proteins by : Robert M. Tanguay

Download or read book The Big Book on Small Heat Shock Proteins written by Robert M. Tanguay and published by Springer. This book was released on 2015-06-15 with total page 610 pages. Available in PDF, EPUB and Kindle. Book excerpt: Based upon a workshop entitled “The Small HSP World” held in Québec 2-5 October 2014. Twenty-five scientists provided chapters for the book. The chapters are from the best scientists currently working in this field. These colleagues include Arrigo, Benesch, Benjamin, Buchner-Haslbeck-Weinkauf, Benndorf, Boelens, Carra, Chang, Currie, Ecroyd, Emanuelsson, Fu, Garrido, Golenhofen, Gusev, Hightower, Kampinga, Lavoie, MacRae, Quinlan, Tanguay, Vierling, Vigh, Weeks and Wu. Briefly, the book starts with the structure of small heat shock proteins, moving to their functions and finishing with their involvement in diseases. Although this is quite broad, the structural aspect will be the unifying theme of the book.

Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging

Author : M. A. Hayat
Publisher : Academic Press
ISBN 13 : 0128094273
Total Pages : 430 pages
Book Rating : 4.1/5 (28 download)

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Book Synopsis Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging by : M. A. Hayat

Download or read book Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging written by M. A. Hayat and published by Academic Press. This book was released on 2016-12-28 with total page 430 pages. Available in PDF, EPUB and Kindle. Book excerpt: Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging is an eleven volume series that discusses in detail all aspects of autophagy machinery in the context of health, cancer, and other pathologies. Autophagy maintains homeostasis during starvation or stress conditions by balancing the synthesis of cellular components and their deregulation by autophagy. This series discusses the characterization of autophagosome-enriched vaccines and its efficacy in cancer immunotherapy. Autophagy serves to maintain healthy cells, tissues, and organs, but also promotes cancer survival and growth of established tumors. Impaired or deregulated autophagy can also contribute to disease pathogenesis. Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and forward-thinking, these books offer a valuable guide to cellular processes while also inciting researchers to explore their potentially important connections. Presents the most advanced information regarding the role of the autophagic system in life and death Examines whether autophagy acts fundamentally as a cell survivor or cell death pathway or both Introduces new, more effective therapeutic strategies in the development of targeted drugs and programmed cell death, providing information that will aid in preventing detrimental inflammation Features recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities, including atherosclerosis and CNS tumors, and their development and treatment Includes chapters authored by leaders in the field around the globe—the broadest, most expert coverage available

Spectrums of Amyotrophic Lateral Sclerosis

Author : Christopher A. Shaw
Publisher : John Wiley & Sons
ISBN 13 : 1119745500
Total Pages : 240 pages
Book Rating : 4.1/5 (197 download)

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Book Synopsis Spectrums of Amyotrophic Lateral Sclerosis by : Christopher A. Shaw

Download or read book Spectrums of Amyotrophic Lateral Sclerosis written by Christopher A. Shaw and published by John Wiley & Sons. This book was released on 2021-04-20 with total page 240 pages. Available in PDF, EPUB and Kindle. Book excerpt: SPECTRUMS OF AMYOTROPHIC LATERAL SCLEROSIS Discover state-of-the-art research findings on ALS from leading authors and editors in the field In Spectrums of Amyotrophic Lateral Sclerosis: Heterogeneity, Pathogenesis & Therapeutic Directions, distinguished researchers and editors Dr. Christopher A. Shaw and Jessica R. Morrice deliver a practical and powerful perspective on Amyotrophic Lateral Sclerosis (ALS) as a heterogeneous spectrum of disorders. This increasingly accepted point-of-view allows researchers and medical professionals to develop better targeted interventions and more precise therapies. In the book, readers will find chapters on a wide variety of critical issues facing ALS researchers and healthcare practitioners treating ALS sufferers, including animal models of ALS, neuronal support cells known to have a pivotal role in ALS, and current challenges in ALS clinical trials, among others. The authors describe pathologic features common to all cases of ALS and why animal models, though crucial, should be interpreted with caution. Finally, multiple genetic and environmental etiologies of the disease are discussed. Readers will also benefit from the inclusion of: A thorough introduction to ALS as a spectrum disease and the implications for models, therapeutic development and clinical trial design Explorations of the genetic basis of ALS, prospective sALS etiologies, and the involvement of microbiome in ALS Discussions of ALS-PDC and environmental risk factors, protein aggregation in ALS, defects in RNA metabolism in ALS, and the non-cell autonomous nature of ALS and the involvement of glial cells Examinations of animal models of ALS and perspectives on previously failed ALS therapeutics and current therapeutic strategies Perfect for clinical neurologists, healthcare providers and caretakers, clinicians, and researchers studying motor neuron disease, Spectrums of Amyotrophic Lateral Sclerosis: Heterogeneity, Pathogenesis & Therapeutic Directions is also an indispensable resource for the neurodegenerative research community, neurology residents, and graduate-level neuroscience students.

Leucine-Rich Repeat Kinase 2 (LRRK2)

Author : Hardy J. Rideout
Publisher : Springer
ISBN 13 : 3319499696
Total Pages : 271 pages
Book Rating : 4.3/5 (194 download)

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Book Synopsis Leucine-Rich Repeat Kinase 2 (LRRK2) by : Hardy J. Rideout

Download or read book Leucine-Rich Repeat Kinase 2 (LRRK2) written by Hardy J. Rideout and published by Springer. This book was released on 2017-03-28 with total page 271 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is the first book to assemble the leading researchers in the field of LRRK2 biology and neurology and provide a snapshot of the current state of knowledge, encompassing all major aspects of its function and dysfunction. The contributors are experts in cell biology and physiology, neurobiology, and medicinal chemistry, bringing a multidisciplinary perspective on the gene and its role in disease. The book covers the identification of LRRK2 as a major contributor to the pathogenesis of Parkinson's Disease. It also discusses the current state of the field after a decade of research, putative normal physiological roles of LRRK2, and the various pathways that have been identified in the search for the mechanism(s) of its induction of neurodegeneration.