Download or read book Innate immunity and neurodegenerative disorders written by Roger A Barker and published by Frontiers E-books. This book was released on 2014-11-03 with total page 88 pages. Available in PDF, EPUB and Kindle. Book excerpt: Inflammation of the brain in the context of neurodegenerative disorders is an area of intense debate and discussion, not least in terms of its pathogenic significance and the extent to which it drives disease processes and pathology. This inflammation can take several forms including innate responses recruiting microglia, humoral responses involving antibody, complement mediated processes and cellular T-cell activation, of which the role and extent of each may differ between diseases. Whilst some diseases have been more intensely linked to inflammation and long-term degeneration (e.g. MS), more traditional chronic neurodegenerative disorders have been thought of in terms of intrinsic neuronal pathology with a secondary innate response. However, it has been described that microglia activation is an early event of many degenerative disorders and evidence is accumulating that it may play a critical role in actually causing pathology and driving disease processes. If true, this would have major therapeutic implications, but what is the evidence that this is the case? The initial observations by Patrick McGeer’s group of post-mortem tissue from patients with Parkinson’s disease revealed the presence of activated brain microglia and has thus lead to the hypothesis that chronic inflammation could participate to neuronal degenerative processes. The significance of these original observations has only been recently revisited, and the development of more powerful tools to study the brain immune response has certainly contributed to this field of research. Chronic inflammation in the brain can take many forms but of particular interest has been the resident microglia and the role they play in this process. In this context, microglia have often been thought to become activated only after the disease has begun and then to contribute minimally to the degenerative process. Emerging new concepts challenge this view by proposing that microglial senescence, for example, may release the disease process and/or accelerate it. In addition, microglia, once activated, can adopt different phenotypes which can be both pro-inflammatory and pro-repair and may impact not only on the healthy adult neuronal population but on those new neurons derived from neurogenic niches of the adult brain. In this Research Topic, we attempt to explore this by first considering the innate immune responses in the brain and the methods by which they can be studied experimentally and in patients with various neurodegenerative disorders. This sets the scene for then discussing a range of different disorders including Alzheimer’s, Parkinson’s, Huntington’s disease and amyotrophic lateral sclerosis. These papers seek to discuss the evidence for an innate immune response and whether this is beneficial or detrimental, as well as its therapeutic implications.
Download or read book Innate immunity and neurodegenerative diseases triggers from self and non self written by Kiran Bhaskar and published by Frontiers Media SA. This book was released on 2023-06-30 with total page 209 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Neuroinflammation and CNS Disorders written by Nicola Woodroofe and published by John Wiley & Sons. This book was released on 2014-04-15 with total page 462 pages. Available in PDF, EPUB and Kindle. Book excerpt: The last decade has seen an upsurge of information on the role of immune responses in neurodegenerative disorders. In many of these diseases it is still unclear whether the innate and adaptive responses are pathogenic or play a role in repair, and thus understanding their precise roles is key to controlling these diseases by designing immune-therapeutic approaches. The connection between many neurological diseases is the realisation that the immune and nervous systems are inextricable linked, and that perturbations in this delicate balance are involved in many disorders. This has opened up new avenues for therapeutic approaches to treatment of CNS inflammatory and neurodegenerative disorders. Neuroinflammation and CNS Disorders brings together the very latest information on the interactions between the immune system and central nervous system. The first section of the book highlights the basic concepts in the field whilst the second section, the main body of the book, covers the role of the immune response in specific disorders of the central nervous system. Neuroinflammation and CNS Disorders will provide an invaluable guide for both researchers and clinicians working in this complex and dynamic field.
Download or read book The Propagation of Neurodegenerative Diseases by Inflammation and Exosomes written by Valerie Sackmann and published by Linköping University Electronic Press. This book was released on 2019-10-16 with total page 60 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative diseases with rates increasing along with the ageing global population. Despite best efforts, we still do not understand the etiopathogenesis of these diseases and there are no effective disease-modifying treatments. Cognitive deficiencies or motor complications that emerge during AD and PD are thought to be the result of the accumulation of misfolded, aggregate-prone proteins, such as amyloid-? (A?) and tau or ?-synuclein (?-syn), respectively. Growing evidence suggests that prefibrillar oligomers of A? and ?-syn (oA? and o?-syn) are key contributors to the progression of these diseases. The progressive accumulation of these proteins leads to a gradual spread of pathology throughout interconnected brain regions, but the mechanisms by which this spreading occurs are still largely unknown. Neuroinflammation has been recognised as an important contributor to neurodegenerative disease. It is hypothesised that a pro-inflammatory environment initiated by the innate immune system, either through activation from A? itself or indirectly through neuronal injury signals in AD. These phenomena are thought to either cause or accelerate AD, such that an anti-inflammatory approach may be neuroprotective. In paper I, we investigated whether different inflammatory environments affected the transfer of oA? between neuron-like cells, in addition to investigating inter- and intracellular protein changes. This study demonstrated that an anti-inflammatory environment reduces the transfer of oA? between cells. We also provide evidence that these cells begin to take on the “phenotype” of the inflammatory milieu, while also demonstrating that the expression profile of endosomal/lysosomal and protein trafficking proteins is altered during these conditions. Small extracellular vesicles called exosomes, which are key players in cell to cell communication, have been proposed to play an influential role in spreading neurodegenerative proteins between cells. Exosomes are small membranous vesicles that are formed by the inward budding of multivesicular bodies (MVBs). These MVBs can then merge with the plasma membrane to be released into the extracellular environment as vesicles, which serve as vehicles for transferring proteins, lipids, and mRNAs between cells. The ESCRT-dependent pathway is the most understood mechanism underlying exosome biogenesis. However, exosomes can also be formed through ESCRT-independent pathways, including through the hydrolysis of sphingomyelin by neutral sphingomyelinase 2 (nSMase2), which produces ceramide. Paper II investigated whether exosomes formed through an ESCRT-independent pathway plays a significant role in the transfer of o?-syn between neuron-like cells. As oxidative stress is a common feature in PD brains, which in turn dysregulates nSMase2 activity, we also tested our model under hypoxic conditions. Inhibition of nSMase2 significantly reduced the transfer of o?-syn between cells but also resulted in decreased ?-syn aggregation. Hypoxia did not influence o?-syn transfer, however, it significantly dysregulated the sphingolipid composition, which may be important for ?-syn binding to exosomes and exosome communication. During AD and PD, there is a noted reduction in the effectiveness of autophagy, a process critical to cellular proteostasis. Recent studies have uncovered shared regulatory mechanisms of exosome biogenesis and autophagy, suggesting that they are closely linked. Previous findings have shown that inhibition of autophagy in AD mice mediates A? trafficking through altering the secretion of A? in MVBs. To further study this effect, we investigated the interplay between autophagy and exosome secretion using ATG7 knock-out x APPNL-F knock-in AD mice in paper III. These autophagy-deficient AD mice had a reduced extracellular A? plaque load, but increased intracellular A?, which was found to be assembled into higher-ordered assemblies. While exosomal secretion was dysregulated in these mice, the amount of A? packaged into the exosomes was unchanged. Lastly, one of the biggest challenges in developing effective treatments for AD is the lack of early diagnosis of living patients. As the connection between exosomes and the spread of neurodegenerative proteins is still relatively new, there remains a diagnostic potential to be explored with exosomes. Paper IV aimed to develop a new diagnostic assay to detect oA? in exosomes isolated from human cerebrospinal fluid. Although exosomal oA? was readily detected in some of these samples, the assay’s sensitivity requires additional optimisation before it can be further validated for the clinic. In summary, the studies presented in this thesis have furthered our understanding of how inflammation, autophagy, and exosomes contribute to the intercellular transmission of AD and PD associated proteins. We have shown that an anti-inflammatory approach may slow down the progression of AD through reducing the transfer of oA? between cells. We also provide novel findings relating to the biogenesis of exosomes, which in turn affected the ability of exosomes to transmit neurodegenerative proteins between cells, and their association with autophagic processes. Finally, we have investigated the feasibility of exosomes as an early AD diagnostic marker. This work has helped to elucidate some of the mechanisms underlying the progression of neurodegenerative diseases, which may be useful targets for the investigation of new therapeutic avenues.
Download or read book Innate Immunity in Health and Disease written by Shailendra K. Saxena and published by BoD – Books on Demand. This book was released on 2021-08-25 with total page 416 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book focuses on various aspects and properties of innate immunity, whose deep understanding is integral for safeguarding the human race from further loss of resources and economies due to innate immune response-mediated diseases. Throughout this book, we examine the individual mechanisms by which the innate immune response acts to protect the host from pathogenic infectious agents and other non-communicable diseases. Written by experts in the field, the volume discusses the significance of macrophages in infectious disease, tumor metabolism, and muscular disorders. Chapters cover such topics as the fate of differentiated macrophages and the molecular pathways that are important for the pathologic role of macrophages.
Download or read book Neural Immune Interactions in Brain Function and Alcohol Related Disorders written by Changhai Cui and published by Springer Science & Business Media. This book was released on 2012-11-14 with total page 587 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent studies have provided clear evidence on the role of neural-immune interactions in normal brain function and neuropathological conditions. Neuroimmune factors, which play an essential role in neuroinflammatory response, have been implicated in the regulation of neuronal function and plasticity. Thus, neural-immune interactions provide a new frame work for understanding the role of the neuroimmune system in normal brain function, neurodevelopment, and a variety of neurological disorders. These advances have a far reaching impact on many areas of neuroscience, including alcohol research. Studies using human alcoholic brains, gene knockout mice, and gene expression profiling have established a clear link between alcoholism and an altered neuroimmune profile. This book integrates emerging knowledge on neural-immune interactions with key discoveries in alcohol research and provides a comprehensive overview of neural-immune interactions in brain function and behavior associated with alcohol use disorders. While Neural–Immune Interaction in Brain Function and Alcohol Related Disorders focuses on neural-immune interactions in areas directly related to alcohol use disorders, it is not intended to be all inclusive. Several areas, including sleep disorders, pain, and cholinergic anti-inflammatory pathways, are not covered as independent chapters but briefly mentioned in the text. The close relevance of these topics to neural-immune interactions and alcohol use disorders warrants future discussion and more research efforts.
Download or read book The Molecular Immunology of Neurological Diseases written by Sunil Kumar and published by Academic Press. This book was released on 2021-02-16 with total page 178 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Molecular Immunology of Neurological Diseases provides a comprehensive review of current updates in molecular immunogenetics of different neurological diseases. Readers will learn about the role of immune cells and their modulation strategies to help in the development of therapeutic approaches for both acute and chronic neurodegenerative disorders. There is no other book available on the topic. It has long been thought that the brain is an immune-privilege organ with very limited immune response. However recent studies have made clear that both systemic 'brain' and peripheral 'blood' immune cell responses play key roles in determining brain pathology in neurodegenerative disorders. This book summarizes the role of immune cell activation in the central nervous system microenvironment in acute and chronic neurodegenerative disorders. In addition, it discusses the key role of immune cells and their modulation strategies for the development of current therapeutic approaches. Discusses the molecular immunogenetics of different neurological diseases Covers strategies for the development of therapeutic approaches Encompasses both acute and chronic neurogenerative disorders Describes the molecular pathogenesis of viral genes in various diseases Features chapters on migraine, muscular dystrophy and cancer
Download or read book Handbook of Infection and Alzheimer s Disease written by J. Miklossy and published by IOS Press. This book was released on 2017-03-10 with total page 420 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer’s disease is one of the biggest emerging public health problems in the world. Although the last four decades have yielded important insights into the pathogenesis of Alzheimer’s disease, its cause is still unclear, and if it is not discovered the world will face an unprecedented healthcare problem by the middle of this century. In recent years, evidence of the microbial origin of various chronic inflammatory disorders – including several neurodegenerative, neuropsychiatric and other systemic disorders – has been steadily growing. Accumulating new and historic observations are providing evidence of an association between Alzheimer’s disease and certain infectious agents, and may offer new opportunities for ground-breaking healthcare solutions. This handbook assembles and connects findings with regard to the infectious origin of Alzheimer’s disease, and the data presented in its chapters deserves the attention of the neuroscience community, physicians and the health departments of governments worldwide by virtue of its amount and quality. This handbook offers a comprehensive overview of the current knowledge regarding the topic of infection and Alzheimer’s disease, which could pinpoint the cause of this disease. Influential diagnosis, treatment and prevention strategies may also emerge from this crucial research area.
Download or read book Target Pattern Recognition in Innate Immunity written by Uday Kishore and published by Springer Science & Business Media. This book was released on 2010-01-01 with total page 220 pages. Available in PDF, EPUB and Kindle. Book excerpt: Target pattern recognition in innate immunity is responsible for the immediate, usually protective, responses shown against invading microorganisms, and it is the principal feature of self and non-self recognition by virtue of the recognition of structures on the microbial pathogens, which are not found on host cells. This is an area that has been very actively researched, over approximately the past 12 years, and therefore this volume provides a timely comprehensive, and up to date, summary of the types and range of cell surface, intracellular, and secreted, host proteins involved in the recognition of microbial products, and of the protective mechanisms triggered as a result of the recognition events. The Toll-like receptors, first described in Drosophila and now well-characterised on human cells, provide an excellent demonstration of the wide range of different microbial products recognised by this family of receptors and of the signalling pathways which are triggered thus leading to induction of inflammatory cytokines and the activation of genes producing antimicrobial products. In addition, several cell surface proteins involved in target pattern recognition have been described on the surfaces of macrophages (macrophage mannose receptor and macrophage scavenger receptors), and on dendritic cells (DEC205), and to be involved with the uptake and clearance of whole microorganisms and polyanioic ligands. Pattern recognition is also utilised by intracellular receptors, with NOD-like receptors in the cytosol recognizing microbial molecules and activating the production of inflammatory cytokines or pathways that induce the production of inflammatory molecules. Secreted proteins, such as the pentraxins, which includes the acute phase reacting, C-reactive protein (CRP) and serum amyloid protein (SAP), and the collectins (mannan binding lectin, lung surfactant protein A and D) and ficolins can also readily recruit killing and clearance systems. Indeed, the serum complement system, which is one of the major defence systems in the bloodstream, is efficiently activated by CR P on its binding to the phosphocholine groups of microbial phospholipids—and the subsequent interaction of the bound CR P with C1q—to give classical pathway activation, or MBL, or ficolin, binding to arrays of mannose or N-acetyl-glucosamine residues, respectively, on the surfaces of microorganisms—to give lectin pathway activation. Also, in addition to the activation and clearance events associated with complement activation by some of the secreted pattern recognition receptors, it is accepted that all these pattern recognition receptors can generally accelerate the uptake and clearance of microbes via phagocytic cells. In view of the growing interest in the cross-talk between innate and adaptive immunity, a thorough understanding of the initial recognition and triggering events, mediated via innate immune receptors, as addressed in this volume, is clearly very useful in helping to also fully understand the mechanisms of activation and control of the adaptive immune system—and to allow a full assessment of the relative roles played by innate immunity and adaptive immunity against a particular infection in higher organisms.
Download or read book Deciphering the Role of Neural Innate Immune Signaling in Aging and Neurodegenerative Disease in Drosophila written by Sinan Sanih Khor and published by . This book was released on 2020 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Inflammation in Heart Failure written by Matthijs Blankesteijn and published by Academic Press. This book was released on 2014-12-05 with total page 221 pages. Available in PDF, EPUB and Kindle. Book excerpt: Inflammation in Heart Failure, edited by W. Matthijs Blankesteijn and Raffaele Altara, is the first book in a decade to provide an in-depth assessment on the causes, symptoms, progression and treatments of cardiac inflammation and related conditions. This reference uses two decades of research to introduce new methods for identifying inflammatory benchmarks from early onset to chronic heart failure and specifically emphasizes the importance of classifying at-risk subgroups within large populations while determining the patterns of cytokines in such classifications. Further, the book details clinical applications of the pathophysiological mechanisms of heart failure, diagnosis and therapeutic strategies. Inflammation in Heart Failure's breadth of subject matter, easy-to-follow structure, portability, and high-quality illustrations create an accessible benefit for researchers, clinicians and students. - Presents updated information and research on the relevant inflammatory mediators of heart failure to aid in targeting future translational research as well as the improvement of early diagnosis and treatment - Provides research into better understanding the different inflammatory mediators that signal the underlying diseases that potentially lead to heart failure - Contains 20 years of research, offering a brief overview of the topic leading to current opinions on, and treatment of, heart failure - Provides a structured, systematic and balanced overview of the role of inflammation in heart failure making it a useful resource for researchers and clinicians, as well as those studying cardiovascular diseases
Download or read book Neuroimmune System written by Arpit Kumar Pradhan and published by CRC Press. This book was released on 2024-11-15 with total page 194 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book explores the intricate connections between the nervous and immune systems in the context of neurodegenerative disorders, offering a comprehensive overview of the bidirectional communication between these systems and their implications for disease progression and therapeutic interventions. The book aims to understand the recent developments in the field of neuroimmune communication. Key Features: In-depth analysis of immunological biomarkers and therapeutic targets for neurodegenerative disorders. Exploration of the role of glial cells in neuroimmune interactions and their dual nature in disease pathology. Examination of short- and long-range interactions between the central nervous system (CNS) and immune system, including hormonal axis and cytokine milieu. Discussion on the impact of microbiota on neural networks and immune responses, highlighting the gut-brain axis and potential therapeutic avenues. Utilization of Drosophila model systems to study neurodegeneration, providing insights into disease mechanisms and potential treatment strategies. Coverage of various neurodegenerative disorders, including Alzheimer’s, Parkinson’s, polyglutamine-related diseases, and tauopathy, with a focus on understanding disease progression and identifying therapeutic targets. The book stands out for its interdisciplinary approach, bridging the fields of neuroscience, immunology, and microbiology to provide a holistic understanding of neurodegenerative diseases. It offers valuable insights into the complex interplay between the nervous and immune systems, shedding light on novel therapeutic avenues for treating these debilitating conditions. Suitable for researchers, clinicians, and students in the fields of neurology, immunology, and microbiology, this book serves as an essential resource for understanding the pathogenesis and treatment of neurodegenerative disorders.
Download or read book Neuroimmune Pharmacology written by Tsuneya Ikezu and published by Springer Science & Business Media. This book was released on 2008-03-21 with total page 850 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neuroimmune pharmacology seeks to harness the immune system to provide pharmacological intervention to combat neurodegenerative diseases. This book provides a comprehensive overview of topics that embrace the link between the immune system and the pathogenesis of neurodegenerative disorders. Results from recent studies strongly suggest that a major part of the process in diseases including Alzheimer’s and Parkinson’s as well as Prion diseases, comes from changes in the innate and adaptive arms of the brain and peripheral immune systems. Thus, the book provides an in-depth study of numerous fields including immunology, pharmacology, neuroscience and neurovirology. It is accompanied by a CD-ROM that includes access to lectures, slide presentations, and question and answers on neuroimmune pharmacology.
Download or read book Innate Immunity Mechanisms in Parkinson Disease written by Mark Stephen Moehle and published by . This book was released on 2015 with total page 197 pages. Available in PDF, EPUB and Kindle. Book excerpt: Parkinson disease (PD) is a late onset, progressive neurodegenerative movement disorder with cardinal symptoms of tremor at rest, bradykinesia, postural instability, and rigidity. These motor symptoms of PD are caused by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). However, despite PDs first modern observation in 1817, little is understood about the causes and molecular mechanisms behind dopaminergic neuron loss. The relatively weak understanding of pathological mechanisms has hindered the development of treatments to slow or halt the progression of PD. However, recently, mounting evidence from post-mortem, imaging, and retrospective studies suggest an important role for inflammation in the etiology of PD. Post-mortem analysis has implicated an elevated level of pro-inflammatory cells and cytokines in the brains and cerebrospinal fluid of patients with PD compared to control. Dopaminergic cells in the SNpc have been suggested to be particularly sensitive to these cells and cytokines found in post-mortem analysis, making the examination of inflammation as a pathological modifier or cause of PD of high therapeutic interest. Familial studies of PD have yielded some clues to target inflammation in the study of PD. From these studies, mutations in leucine rich repeat kinase 2 (LRRK2) have been shown to be the largest genetic cause of PD. Outside of PD, LRRK2 is genetically and biochemically linked to inflammation. Genetically, LRRK2 is associated with inflammatory disorders such as leprosy and Crohn's Disease through genome wide association studies. At a biochemical level, expression studies show very high LRRK2 protein abundance in innate immune cells. Genetic or pharmacological manipulation of LRRK2 results in altered immune response, making LRRK2 an excellent mechanism to study inflammation in PD. Throughout this dissertation, we will utilize genetic manipulations of LRRK2 to knockout or overexpress kinase active forms of LRRK2 coupled with robust models of inflammation both in vitro and in vivo to understand how LRRK2 influences immune cells and provide insight into inflammatory mechanisms in PD.
Download or read book Clinical Immunology written by Robert R. Rich and published by Mosby Incorporated. This book was released on 2008 with total page 1578 pages. Available in PDF, EPUB and Kindle. Book excerpt: Offers answers to challenges in clinical immunology. This book contains immunology knowledge and includes a companion web site to give you two ways to find the answers you need.
Download or read book Toll like Receptors Roles in Infection and Neuropathology written by Tammy Kielian and published by Springer Science & Business Media. This book was released on 2009-08-19 with total page 198 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mammalian Toll-like receptors (TLRs) were first identified in 1997 based on their homology with Drosophila Toll, which mediates innate immunity in the fly. In recent years, the number of studies describing TLR expression and function in the nervous system has been increasing steadily and expanding beyond their traditional roles in infectious diseases to neurodegenerative disorders and injury. Interest in the field serves as the impetus for this volume in the Current Topics in Microbiology and Immunology series entitled "Toll-like receptors: Roles in Infection and Neuropathology". The first five chapters highlight more traditional roles for TLRs in infectious diseases of the CNS. The second half of the volume discusses recently emerging roles for TLRs in non-infectious neurodegenerative diseases and the challenges faced in these models with identifying endogenous ligands. Several conceptual theories are introduced in various chapters that deal with the dual nature of TLR engagement and whether these signals favor neuroprotective versus neurodegenerative outcomes. This volume should be informative for both experts as well as newcomers to the field of TLRs in the nervous system based on its coverage of basic TLR biology as well as specialization to discuss specific diseases of the nervous system where TLR function has been implicated. A must read for researchers interested in the dual role of these receptors in neuroinfection and neurodegeneration.
Download or read book Micro and Nanotechnology in Vaccine Development written by Mariusz Skwarczynski and published by William Andrew. This book was released on 2016-09-20 with total page 462 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a comprehensive overview of how use of micro- and nanotechnology (MNT) has allowed major new advance in vaccine development research, and the challenges that immunologists face in making further progress. MNT allows the creation of particles that exploit the inherent ability of the human immune system to recognize small particles such as viruses and toxins. In combination with minimal protective epitope design, this permits the creation of immunogenic particles that stimulate a response against the targeted pathogen. The finely tuned response of the human immune system to small particles makes it unsurprising that many of the lead adjuvants and vaccine delivery systems currently under investigation are based on nanoparticles. - Provides a comprehensive and unparalleled overview of the role of micro- and nanotechnology in vaccine development - Allows researchers to quickly familiarize themselves with the broad spectrum of vaccines and how micro- and nanotechnologies are applied to their development - Includes a combination of overview chapters setting out general principles, and focused content dealing with specific vaccines, making it useful to readers from a variety of disciplines
