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Innate immunity and neurodegenerative disorders

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193103 Year: Pages: 87 DOI: 10.3389/978-2-88919-310-3 Language: English
Publisher: Frontiers Media SA
Subject: Psychiatry --- Therapeutics --- Neurology --- Medicine (General) --- Science (General)
Added to DOAB on : 2016-02-05 17:24:33
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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.

9 Reading Galen in Byzantium (Book chapter)

Book title: Greek Medical Literature and its Readers

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ISBN: 9781472487919 9781351205276 Year: Pages: 53 Language: English
Publisher: Taylor & Francis
Subject: Medicine (General)
Added to DOAB on : 2018-02-27 11:01:48
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In this chapter, I shall focus on the Galenic corpus, whose dissemination in the Byzantine world was widespread and influential; in particular, I have chosen to&#xD;examine the various revivals of Galen’s Therapeutics to Glaucon, which was copied&#xD;widely. A number of authors produced commentaries based on this treatise and&#xD;some were invariably influenced by it in composing their own works throughout the&#xD;Byzantine era (AD 330–1453).4 My study is not exhaustive, but rather I shall select&#xD;specific examples of interest from the various forms of evidence. First, I shall provide&#xD;some basic introductory details on Galen’s Therapeutics to Glaucon, followed&#xD;by a section on its circulation and textual transmission in Byzantium. Then, I shall&#xD;go on to discuss its revival by Byzantine medical authors into two further sections;&#xD;the first focuses on commentaries and the second deals with medical handbooks.

2015: Which new directions for Alzheimer's disease?

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195350 Year: Pages: 122 DOI: 10.3389/978-2-88919-535-0 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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According to the World Health Organization, more than 40 million people in the world are affected with dementia. To date, 60-70% of the cases of dementia are attributed to the Alzheimer's disease (AD). This neurodegenerative disorder gradually takes place over a period of at least 20 years before the onset of symptoms, which are impaired memory, apathy and depression. The characteristics of AD consist in neurofibrillary tangles (intraneuronal aggregates of hyperphosphorylated tau proteins) and senile plaques (dense extraneuronal deposits composed of amyloid ß (Aß)). The other features linked to these two core pathological hallmarks of AD are inflammation, oxidative stress, progressive synaptic and neuronal loss. In past years, some of the emerging therapeutic strategies against AD were employed to deal with the pathological hallmarks of the disease. Science teams all over the world try to restore the tau phosphorylation equilibrium. Their purpose is to interfere with the aggregation of tau and decrease its amount of proteins per se as well. Furthermore, they are trying either to stimulate the elimination processes of the aggregated tau proteins or to stop the formation of Aß peptides. This could be reached by the stimulation of the classic techniques of protein degradation such as the autophagic pathway, or by the targeted immunotherapy. In this Research Topic, we wish to summarize and review the etiology of AD and the related therapeutic opportunities for the next decades. To fully understand the precise mechanisms underlying AD, research findings, reviews, new insights and new approaches include AD and related tauopathies, tau phosphorylation balance, pharmacological compounds against AD, neuroprotection strategies and new therapeutic ways but also risk factors for AD and AD genetic information are included in this issue.

Enterotoxins: Microbial Proteins and Host Cell Dysregulation

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ISBN: 9783038421634 9783038421641 Year: Pages: 306 DOI: 10.3390/books978-3-03842-164-1 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Added to DOAB on : 2016-06-03 11:14:38
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Pathophysiology and Imaging Diagnosis of Demyelinating Disorders

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ISBN: 9783038429432 9783038429449 Year: Pages: X, 168 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Neurology
Added to DOAB on : 2018-06-27 15:51:32
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Demyelinating disorders are chronic autoimmune disorders characterized by inflammation, demyelination, axonal degeneration, and neuronal loss. They have complex pathophysiology and diverse clinical presentations. The etiology of these disorders lies in the interaction between genetic and environmental factors. Due to the complexity in pathophysiology and presentation, diagnosis and treatment can be challenging. Advanced technology, including modern imaging techniques, as well as optical coherence tomography (OCT), enrich our understanding of the disease process, improve diagnostic accuracy, and may guide treatment decisions.

Computational and Experimental Approaches in Multi-Target Pharmacology

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452521 Year: Pages: 122 DOI: 10.3389/978-2-88945-252-1 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Therapeutics
Added to DOAB on : 2018-02-27 16:16:44
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The next frontier in pharmacology is the development of multi-target strategies in which pathological processes are controlled by pharmacologically manipulating them at many different points at once. Designing multi-target strategies will require deep understanding of the complex physiology that underlies pathological processes. It will also require the development of single drugs with multiple targets, or combinations of drugs with compatible pharmacokinetics that work synergistically to maximize desirable effects while minimizing unwanted side effects. This e-Book contains ten original articles, each addressing a different aspect of this challenge. Together they open new perspectives and show the way forward in the development of multi-target therapeutics.

Molecular Chaperones and Neurodegeneration

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453429 Year: Pages: 180 DOI: 10.3389/978-2-88945-342-9 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2018-02-27 16:16:45
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Molecular chaperones or heat-shock proteins (HSPs) play essential roles in safeguarding structural stability and preventing misfolding and aggregation of proteins, and maintaining the proteome functionality in the cell. For over two decades until the present time, new functions have been discovered and several molecular mechanisms have been elucidated for many chaperones, while the field is being continuously challenged by new open questions. Probably as a consequence of the increasing research on the molecular bases of neurodegenerative diseases, and the realisation that many such disorders are linked to protein misfolding processes, unleashing the roles and mechanisms of chaperones in the context of neurodegeneration has become a prime scientific goal. This e-book contains a diversity of reviews, perspective and original research articles highlighting the importance and potential of this emerging subject.

Recent Progress in Bunyavirus Research

Authors: ---
ISBN: 9783038423935 9783038423928 Year: Pages: VIII, 224 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology
Added to DOAB on : 2017-06-14 11:52:43
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The Bunyaviridae is the largest family of RNA viruses, with over 350 isolates worldwide distributed into five genera (i.e., Hantavirus, Orthobunyavirus, Nairovirus, Tospovirus, and Phlebovirus). Many of these viruses are significant human or agricultural pathogens. The increasing number of reports on new emerging bunyaviruses and infection episodes makes it essential that we obtain a comprehensive understanding of bunyaviruses and their infection mechanisms. Although all bunyaviruses possesses a tripartite, negative-sense (or ambi-sense) RNA genome, they exhibit substantial differences in their structure, genome organization and replication strategies, which make functional interpolation across genus boundaries difficult.Fortunately, the bunyavirus field has witnessed many exciting new findings and breakthroughs in recent years. These discoveries span a wide spectrum of research areas, including structural characterization of viruses and viral proteins, the identification of new viruses, investigations into host switch and vectors of transmission, genome-based analysis of virus evolution and phylogenetic lineages, the development of new research tools, such as replicons and reverse genetics, molecular characterization of the virus life cycle at the cell level (i.e., cell entry, replication, transcription, translation, genome packaging, reassortment, and virus assembly, etc.), studies of virus–host interactions and host antiviral defense, the development of vaccines/drugs and the use of bunyaviruses for novel applications.This book includes both research and review papers that together provide a glimpse into the latest research on bunyaviruses and, at the same time, highlight some of the important research achievements made in recent years. Study topics of both a fundamental and applied nature are collated. An informed perspective for future research directions is provided and can stimulate research in some of the understudied areas.

Roles of NF-κB in Cancer and Their Therapeutic Approaches

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ISBN: 9783038971177 9783038971184 Year: Pages: X, 330 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Oncology --- Biology
Added to DOAB on : 2018-08-15 10:52:09
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Although mortality rates have declined in recent years, the majority of cancers are still difficult to treat and the medical need for better cancer treatment is evident. The current anticancer armamentarium includes many active agents that are applied across tumor types. However, most of these broadly-active anticancer drugs have a small therapeutic index and barely discriminate between malignant and normal cells. In recent years the focus has shifted to the development of rationally designed, molecularly-targeted therapy for the treatment of a specific cancer, therefore offering the promise of greater specificity coupled with reduced systemic toxicity. NF-kB transcription factor family as emerged as such a promising target for cancer therapy. This Special Issue will explore the routes from NF-kB basic research, cancer research and oncogenomics into the development of NF-kB-based cancer therapeutics and biomarkers.We invite research and review papers in any area of the NF-kB field that are related, but not limited to, fundamental understanding of NF-kB signaling pathways, gene expression profiling, epigenetic regulation, diagnostic, prognostic and pharmacogenomic biomarkers, molecular targets driving the progression of human cancers, cancer drug development on these targets, clinical trial with new agents, and validation in animal models.We hope that this Special Issue reflects the exciting era that we are living in with respect to the field of NF-kB and its applications in cancer research.

PrPSc Prions: State of the Art

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ISBN: 9783038973089 9783038973096 Year: Pages: 210 DOI: 10.3390/books978-3-03897-309-6 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General) --- Biology
Added to DOAB on : 2018-11-07 10:54:14
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Prion diseases, or transmissible spongiform encephalopathies (TSEs), are a group of fatal and transmissible neurodegenerative disorders characterized by long incubation periods, misfolded prion protein (PrP) deposition, and usually spongiform vacuolation. These devastating diseases affect many mammals, with the best known examples being Creutzfeldt–Jakob disease (CJD), fatal familial insomnia (FFI), or Kuru in humans; and scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, and chronic wasting disease (CWD) in cervids. Despite major achievements in research of TSEs, there are still many unresolved key issues that hamper the development of effective therapies. However, the last decade has been particularly prolific in advances in the prion field. Among others, prion propagation in vitro has been achieved, leading to new diagnostic methods; the basic architecture of infectious prions has been deciphered; new prion disease types have been described in humans and other animals; and prion disorders have emerged in places that had not previously reported the disorders, as is the case for CWD in Europe.This Special Issue will focus on the state of the art of our knowledge of PrPSc: on what we know about its structure and propagation, the basis of strains and transmission barriers, the mechanisms of PrPSc toxicity, the possible function of PrPSc’s properly folded precursor, PrPC and its evolutionary history, and recent technical breakthroughs in diagnostics and therapy development among other key aspects of PrPSc prion biology.

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