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Dual role of microglia in health and disease: pushing the balance towards repair

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194926 Year: Pages: 101 DOI: 10.3389/978-2-88919-492-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2015-11-16 15:44:59
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Microglial cells play a vital role in the innate immune response occurring in the Central Nervous System (CNS). Under physiologic conditions, microglia dynamically patrol the brain parenchyma and participate in the remodeling of active neuronal circuits. Accordingly, microglia can boost synaptic plasticity by removing apoptotic cells and by phagocytizing axon terminals and dendritic spines that form inappropriate neural connections. Upon brain and spinal cord injury or infection, microglia act as the first line of immune defense by promoting the clearance of damaged cells or infectious agents and by releasing neurotrophins and/ or proneurogenic factors that support neuronal survival and regeneration.Recently, two main pathways were suggested for microglia activation upon stimuli. Classical activation is induced by Toll-like receptor agonists and Th1 cytokines and polarizes cells to an M1 state, mainly leading to the release of TNF-alpha, IL-6 and nitric oxide and to grave neural damage. Alternative activation is mediated by Th2 cytokines and polarizes cells to an M2a state inducing the release of antiinflammatory factors. These findings have further fueled the discussion on whether microglia has a detrimental or beneficial action (M1 or M2-associated phenotypes, respectively) in the diseased or injured CNS and, more importantly, on whether we can shift the balance to a positive outcome.Although microglia and macrophages share several common features, upon M1 and M2 polarizing conditions, they are believed to develop distinct phenotypic and functional properties which translate into different patterns of activity. Moreover, microglia/macrophages seem to have developed a tightly organized system of maintenance of CNS homeostasis, since cells found in different structures have different morphology and specific function (e.g. meningeal macrophages, perivascular macrophages, choroid plexus macrophages). Nevertheless, though substantial work has been devoted to microglia function, consensus around their exact origin, their role during development, as well as the exact nature of their interaction with other cells of the CNS has not been met.This issue discusses how microglial cells sustain neuronal activity and plasticity in the healthy CNS as well as the cellular and molecular mechanisms developed by microglia in response to injury and disease. Understanding the mechanisms involved in microglia actions will enforce the development of new strategies to promote an efficient CNS repair by committing microglia towards neuronal survival and regeneration.

Nicotinic Acetylcholine Receptor Signaling in Neuroprotection

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ISBN: 9789811084874 9789811084881 Year: Pages: 191 DOI: https://doi.org/10.1007/978-981-10-8488-1 Language: English
Publisher: Springer Grant: Smoking Research Foundation
Subject: Neurology
Added to DOAB on : 2018-06-29 14:19:40
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This open access book presents the roles and mechanisms of signal transduction triggered by nicotinic acetylcholine receptors (nAChRs) stimulation in neuroprotection against toxic effects of risk factors of neurodegenerative diseases. Accumulating evidence suggests that nAChRs in the CNS play important roles not only in excitatory neurotransmission but also in neuronal survival and related functions. Neuroprotection mediated by nAChRs in neurodegenerative diseases such as Alzheimer's disease is the major topic of this book. In response to rapidly evolving areas in clinical and laboratory neuropharmacology and neurochemistry, this volume provides in-depth coverage of neuroprotection in basic research and future developments in the clinical application of effective neuroprotective strategies in neurodegenerative diseases. This work appeals to both basic and clinical researchers in several fields, such as neuroscience, neurology, and pharmacology.

Molecular Diagnostics in the Detection of Neurodegenerative Disorders

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451944 Year: Pages: 90 DOI: 10.3389/978-2-88945-194-4 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Medicine (General) --- Science (General)
Added to DOAB on : 2017-10-13 14:57:01
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Neurodegeneration is characterized by the progressive loss of neural tissue that result in various neurodegeneration-initiated cerebral failures and complex diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease. All these medical conditions are accompanied by the disruption of blood-brain barrier (BBB). The BBB is an interface, separating the brain from the circulatory system and protecting the central nervous system from potentially harmful chemicals while regulating transport of essential molecules and maintaining a stable environment. Owing to the inability of the neurons to regenerate on their own after neurodegeneration or severe damage to the neural tissue, neurodegenerative disorders do not have natural cures on their own. Neuroregeneration is a viable way to curb neurodegeneration. One of the current approaches is stem cell-based therapy that has been shown to be potentially helpful for the application of neuronal cell replacement for neuroregeneration. It is vital that the neurodegenerative disorder being detected at an early stage as it can provide a chance for treatment that may be helpful to prevent further progression of the fatal disease. Thus, research has focused on developing effective non-invasive diagnostic methods for early detection of these disorders. Molecular diagnostics can provide a powerful method to detect and diagnose various neurological disorders. Such diagnosis can enhance early detection, provide subsequent medical counsel based on medical pathway, as well as to gain better insight of neurogenesis and hopefully eventual cure of the neurodegenerative diseases. With research reports, reviews, mini-reviews and commentary, this research topic covers a wide range of areas in neurodegeneration research, including diagnosis and prognosis; regulating central nervous system; biomarkers and brain injury induced neurobehavioral outcomes among other timely reports on neurodegeneration.

Human and Animal Models for Translational Research on Neurodegeneration: Challenges and Opportunities From South America

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454945 Year: Pages: 217 DOI: 10.3389/978-2-88945-494-5 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2019-01-23 14:53:42
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Neurodegenerative diseases are the most frequent cause of dementia, representing a burden for public health systems (especially in middle and middle-high income countries). Although most research on this issue is concentrated in first-world centers, growing efforts in South America are affording important breakthroughs. This emerging agenda poses new challenges for the region but also new opportunities for the field. This book aims to integrate the community of experts across the globe and the region, and to establish new challenges and developments for future investigation. We present research focused on neurodegenerative research in South America. We introduce studies assessing the interplay among genetic, neural, and behavioral dimensions of these diseases, as well as articles on vulnerability factors, comparisons of findings from various countries, and works promoting multicenter and collaborative networking. More generally, our book covers a broad scope of human-research approaches (behavioral assessment, neuroimaging, electromagnetic techniques, brain connectivity, peripheral measures), animal methodologies (genetics, epigenetics, proteomics, metabolomics, other molecular biology tools), species (all human and non-human animals, sporadic, and genetic versions), and article types (original research, review, and opinion papers). Through this wide-ranging proposal, we hope to introduce a fresh approach to the challenges and opportunities of research on neurodegeneration in South America.

Microglial Polarization in the Pathogenesis and Therapeutics of Neurodegenerative Diseases

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455256 Year: Pages: 327 DOI: 10.3389/978-2-88945-525-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2019-01-23 14:53:42
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Microglia-mediated neuroinflammation is one of the shared prominent hallmarks among various forms of neurodegeneration. Depending on the milieu in which microglia become activated, the polarization of microglia shows to be heterogeneous with diverse functional phenotypes that range from pro-inflammatory phenotypes to immunosuppressive phenotypes. Therefore, targeting microglial polarization holds great promise for the treatment of neurodegeneration.This eBook focuses on the potential mechanisms of microglial polarization that are critically associated with a broad spectrum of neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), Traumatic brain injury (TBI), glaucomatous neurodegeneration and prion diseases. This topic also involves the therapeutic targeting of microglial polarization by nutritional and pharmacological modulators. Moreover, this topic describes advanced technologies employed for studying microglia. Age-related changes in microglia functions are also discussed.Overall, this eBook provides comprehensive understandings of microglial polarization in the course of neurodegeneration, linking with aging-related microglial alterations and technologies developed for microglial studies. Hopefully, it will also give comprehensive insights into various aspects of therapeutic treatment for neurodegeneration, through targeting microglial polarization.

Clinical use of biomarkers in neurodegenerative disorders

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194001 Year: Pages: 122 DOI: 10.3389/978-2-88919-400-1 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-12-10 11:59:06
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The prevalence of neurodegenerative disorders is increasing dramatically and one of the major challenges today is the need of early and accurate diagnosis, the other is the need of more effective therapies -in turn the development of such therapies also requires early and accurate diagnosis-. The main hope for an earlier and more accurate diagnosis comes from the use of biomarkers. Much research is being done trying to solve the many interrogates related to the role of biomarkers in clinical practice, including the early diagnosis, differential diagnosis and follow-up of neurodegenerative disorders. This is a field where translational research is intense enough to make this topic interesting for basic researchers and clinicians. Indeed, the amount and quality of articles received in response to the call for contributions was very good. This eBook contains a good amount of high quality articles devoted to diverse techniques across several neurodegenerative disorders from different perspectives, including original reports, reviews, methods reports and opinion letters on biochemical biomarkers in biological fluids, neuroimaging techniques and multidimensional approaches linking clinical findings with biomarkers. The disorders covered are also diverse: Alzheimer’s disease, Frontotemporal Dementia, Dementia with Lewy Bodies, Huntington’s disease, Parkinson’s disease among others. As we can learn from articles in this Research Topic, biomarkers are allowing us to expand the knowledge on the biological and anatomical basis of neurodegenerative diseases and to implement diagnostic techniques in clinical practice and clinical trials.

Neuropsychology and Neuropsychiatry of Neurodegenerative Disorders

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197385 Year: Pages: 190 DOI: 10.3389/978-2-88919-738-5 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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This book compiles all articles within the Research Topic "Neuropsychology and neuropsychiatry of neurodegenerative disorders" published in the journal Frontiers in Aging Neuroscience. The call was launched in 2014 and closed in 2015 with 21 articles published. Papers deal on several important topics of neuropsychology -such as language and visuospatial functions- and neuropsychiatry - such us the emotional or motivational spheres - , and the interphase between them. There are also articles on psychometry, brain morphometry, brain connectivity, diagnostic tests and interventional studies. All these articles are focused on neurodegenerative conditions, mostly Alzheimer’s disease and Parkinson’s disease. Interestingly, several articles addressed the early stages of these diseases. All together, this Research Topic provides a rich perspective of the research made today around neuropsychological and neuropsychiatric aspects of neurodegenerative diseases. We hope readers enjoy this collection of articles.

Golgi Pathology in Neurodegenerative Diseases

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197576 Year: Pages: 119 DOI: 10.3389/978-2-88919-757-6 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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The Golgi apparatus is a central organelle that lies at the heart of the secretory pathway. It ensures post-translational protein modifications such as glycosylation and cleavage as well as protein sorting to neuronal axons and dendrites. Structural and functional alterations of the Golgi apparatus (fragmentation and atrophy), which are collectively termed Golgi pathology, are now recognized as a constant feature of many neuro-degenerative diseases. However, the molecular mechanisms underlying these changes and their precise relevance to neurodegeneration have not yet been completely elucidated. This eBook contains 13 reviews that address the molecular mechanisms of Golgi pathology in Parkinson and Alzheimer diseases, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophies, and discuss their potential relevance to the pathological loss of neuronal cell bodies, axons and synapses.

Gene Silencing and Editing Strategies for Neurodegenerative Diseases

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455515 Year: Pages: 115 DOI: 10.3389/978-2-88945-551-5 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2019-01-23 14:53:42
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Neurodegenerative diseases (NDs) are a heterogeneous group of disorders affecting the central nervous system. Despite significant differences in their causes, neuropathological abnormalities, and clinical outcomes, some similarities can be found among them, as for example: 1) frequent aggregation and deposition of misfolded proteins, 2) common molecular mechanisms leading to neurodegeneration, and 3) certain overlap in symptoms and clinical features. To date, there is no cure that could stop or delay the progression of these diseases. The advent of advanced gene therapy techniques such as gene silencing and gene editing opened a new avenue for the development of therapeutic strategies for NDs.The discovery of the RNA interference (RNAi) mechanism, in 1998, by Andrew Fire and Craig Mello allowed an important boost to the gene therapy field, providing a potential therapeutic strategy to treat inherited dominant genetic disorders. The use of small RNA sequences to control the expression of disease-causing genes rapidly implemented in the preclinical studies for different diseases. In the field of NDs, several successful studies using this technology proved its potential as a therapeutic option. However, issues like the type of delivery system (non-viral versus viral) or the potential toxicity of the small RNA molecules, made the translation of gene silencing therapeutics to human application very slow and difficult.Recently, a new hope in the gene therapy field emerged with the development of gene editing techniques like TALENs or CRISPR/Cas9 systems. The opportunity of editing or deleting gene sequences drove the scientific community euphoric, with an enormous increase in the number of published studies using this type of techniques. Recently, the first clinical trial using one of these systems was approved in China. For NDs, gene-editing technology also represents an important therapeutic option, and the first preclinical studies are now being published, showing the potential accomplishment for this technology.

Adult neurogenesis twenty years later: physiological function versus brain repair

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194940 Year: Pages: 120 DOI: 10.3389/978-2-88919-494-0 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-11-16 15:44:59
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The discovery that mammalian brains contain neural stem cells which perform adult neurogenesis - the production and integration of new neurons into mature neural circuits - has provided a fully new vision of neural plasticity. On a theoretical basis, this achievement opened new perspectives for therapeutic approaches in restorative and regenerative neurology. Nevertheless, in spite of striking advancement concerning the molecular and cellular mechanisms which allow and regulate the neurogenic process, its exploitation in mammals for brain repair strategies remains unsolved. In non-mammalian vertebrates, adult neurogenesis also contributes to brain repair/regeneration. In mammals, neural stem cells do respond to pathological conditions in the so called "reactive neurogenesis", yet without substantial regenerative outcome. Why, even in the presence of stem cells in the brain, we lack an effective reparative outcome in terms of regenerative neurology, and which factors hamper the attainment of this goal? Essentially, what remains unanswered is the question whether (and how) physiological functions of adult neurogenesis in mammals can be exploited for brain repair purposes.

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