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Never-resting microglia: physiological roles in the healthy brain and pathological implications

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193691 Year: Pages: 172 DOI: 10.3389/978-2-88919-369-1 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-11-19 16:29:12
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Microglia are largely known as the major orchestrators of the brain inflammatory response. As such, they have been traditionally studied in various contexts of disease, where their activation has been assumed to induce a wide range of detrimental effects. In the last few years, a series of discoveries have challenged the current view of microglia, showing their active and positive contribution to normal brain function. This Research Topic reviewed the novel physiological roles of microglia in the developing, mature and aging brain, under non-pathological conditions. In particular, this Research Topic discussed the cellular and molecular mechanisms by which microglia contribute to the formation, pruning and plasticity of synapses; the regulation of adult neurogenesis as well as hippocampal learning and memory; among other important roles. Because these novel findings defy our understanding of microglial function in health as much as in disease, this Research Topic also summarized the current view of microglial nomenclature, phenotypes, origin and differentiation, and contribution to various brain pathologies. Additionally, novel imaging approaches and molecular tools to study microglia in their non-activated state have been discussed. In conclusion, this Research Topic sought to emphasize how the current research in neuroscience is challenged by never-resting microglia.

Mechanisms of Innate Neuroprotection

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199297 Year: Pages: 138 DOI: 10.3389/978-2-88919-929-7 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Neurology --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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As clinical trials of pharmacological neuroprotective strategies in stroke have been disappointing, attention has turned to the brain's own endogenous strategies for neuroprotection. Two endogenous mechanisms have been recently characterized, ischemic preconditioning and ischemic postconditioning. In the present topic newly characterized mechanisms involved in preconditioning- and postconditioning- neuroprotection will be discussed. The understanding of the mechanisms involved in the neuroprotective pathways induced by preconditioning and postconditioning will be clinically relevant for identifying new druggable target for neurodegenerative disorder therapy. Furthermore, the importance of these neuroprotective strategies resides in that it might be easily translatable into clinical practice. Therefore, the data presented here will highlight the capacity of ischemic preconditioning and postconditioning to be of benefit to humans.

Unraveling Neuroprotective and Neurodegenerative Signals in Neurodegeneration

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199563 Year: Pages: 131 DOI: 10.3389/978-2-88919-956-3 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2016-01-19 14:05:46
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Proteinopathy is a collective term used to classified neurodegenerative diseases associated with the progressive accumulation of toxic protein molecules in specific brain regions. Alzheimer’s disease (AD) is a well-known proteinopathy characterize by the accumulation of A peptides and tau proteins. The accumulation of these toxic molecules in the brain starts many years before any clinical presentation, being the onset in the range of 65 to 72 years of age. Therefore, age is considered a risk factor due, in part, to the loss of molecular competence to clear the brain from these toxic protein molecules. This fact, supported by years of research, demonstrates that brain cells activate a neuroprotective mechanism upon detection of a pathobiological signal that (if the detrimental conditions persist) precedes the activation of the neurodegeneration pathway. The progressive brain region specific neuronal death in neurodegenerative diseases also indicates that the transition from neuroprotection to neurodegeneration is individually triggered in cells of the affected brain region. Thus, molecular understanding of the pathophysiology associated with proteinopathies needs to take in consideration this intricate transition process, especially when genomics and proteomics approaches are used. Research directed to understand the pathogenesis and pathophysiology of neurodegenerative diseases uncovered the putative role of different molecular mechanisms associated with neurodegeneration. Among the molecular mechanisms identified are proteolysis, epigenetics, microRNA, transcriptional regulation, innate and adaptive immune system, phagocytosis and autophagocytosis, exo/endocytosis, unfolded protein response, cytoskeleton defects, unregulated signaling molecules (i.e. kinases and phosphatases), trafficking molecules, cell cycle, neurogenesis/neurodevelopment, among others. Interestingly, all these molecular mechanisms have been identified through the analysis of tissue from animal models or human post-mortem pathologically confirmed cases, but their specific role in neurodegeneration is still unclear. Thus, it is plausible to consider that all these pathways play a role at a particular phase of the neurodegeneration process or, simply, are drive by the agonal state of the tissue examined. Hence, an important conundrum that researchers face today is the use of heterogeneous brain tissue samples in the quest to identify biomarkers associated with the pathogenesis or pathophysiology of neurodegenerative diseases. At this junction of the neurodegeneration field, this research topic aim to critically assess the current literature on molecular mechanisms associated with neurodegeneration and the approaches used to dissect their putative pathophysiological role. The studies could include the interplay between neuroprotective and neurodegenerative signals in neurodegeneration, dissecting the molecular role of identified biomarkers, bioinformatics tools that facilitate data mining, dissecting pathways or molecular mechanisms, stages of protein aggregation (oligomers vs tangles; who did it?), aging brain and brain fitness (A natural selection process), adaptive protein response to environmental insults and cellular signals, expression profile associated with neurological disorders and health. Therefore, this Research Topic is expected to cover a wide range of subjects related to unravel the interplay between neuroprotective and neurodegenerative signals in neurodegeneration.

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.

CNS Recovery after Structural and/or Physiological/Psychological Damage

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450404 Year: Pages: 107 DOI: 10.3389/978-2-88945-040-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2018-02-27 16:16:44
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There is an assumption that environmental threats could cause important damages in central nervous system. As a consequence, several forms of brain structural plasticity could be affected. The environmentally mediated risks include generally physical (such as brain and spinal cord injury) and psychological / psychosocial influences (e.g. stress). In general, the response of the organism to these environmental challenges passes via adaptive responses to maintain homeostasis or functional recovery. These processes engage the immune system, the autonomic nervous system (ANS) besides the hypothalamo-hypophyseo-adrenal (HPA) axis via specific hormones, neurotransmitters, neuropeptides and other factors which participate, in several cases, in structural remodeling in particular brain areas. To what extent a brain and / or spinal cord recovery after structural and / or physiological / psychological damage could occur and by which mechanisms, this is the goal of this Research Topic. It concerns neurogenesis, growth factors and their receptors, and morphological plasticity. On the other hand, it is well known that stress experienced an obvious impact on many behavioral and physiological aspects. Thus, environmental stress affects neuroendocrine structure and function and hence such aspects may influence brain development. Knowing normal organization of neurotensin receptors’ system during postnatal development in human infant will help understanding the dysfunction of this neuropetidergic system in “sudden infant syndrome” victims. Stress could affect also other non-neuroendocrine regions and systems. GABA is one of the classical neurotransmitter sensitive to stress either when applied acutely or repetitively as well as its receptor GABAA. Furthermore, the modulation of this receptor complex notably by neurosteroids is also affected by acute stress. These steroids seem to play a role in the resilience retained by the stressed brain. Their modulatory role will be studied in the context of chronic stress in rats. Finally, one of the major impacts of stress besides changes in psychological behavior is the alteration of food intake control causing in final eating disorders. This alteration is the result of changes occurring in activity of brain regions involved in stress responses (principally HPA and ANS) and which are also involved in food intake control. The series of studies presented here, will try to explain how different stress paradigms affect this function and the eventual interactions of glucocorticoids with orexigenic (neuropetide Y: NPY/Agouti Related Peptide: AgRP) and anorexigenic peptides (Pre-opiomelanocortin peptide: POMC/Cocaine Amphetamine regulatory Transcript peptide: CART).

Promiscuous functions of the prion protein gene family

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196050 Year: Pages: 113 DOI: 10.3389/978-2-88919-605-0 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Biology
Added to DOAB on : 2016-08-16 10:34:25
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The cellular prion protein PrPC is a ubiquitous GPI-anchored protein. While PrPC has been the focus of intense research for its involvement in a group of neurodegenerative disorders known as transmissible spongiform encephalopathies (TSE), much less attention has been devoted to its physiological function. This notably relates to the lack of obvious abnormalities of mice, goat or cattle lacking PrPC. This apparently normal phenotype in these PrPC-deficient animals however contrasts with the very high degree of conservation of the prion protein gene (Prnp) in mammalian species (over 80%), and the presence of genes with similarities to Prnp in birds, reptiles, amphibians and fish. This high conservation together with its ubiquitous expression, - albeit at highest levels in the brain-, suggest that PrPC has major physiological functions. Dissecting PrPC function is further complicated by the occurrence, in mammals, of two potentially partially redundant homologues, Doppel, and Shadoo. The biological overlaps between members of the prion protein family are still under investigation and much debated. Similarly, although in vitro analyses have suggested various functions for PrPC, notably in cell death and survival processes, some have yielded conflicting results and/or discrepancies with in vivo studies. This Research Topic brings together the accumulated knowledge regarding the biological roles of the prion protein family, from the animal to the molecular scale.

Molecular Chaperones and Neurodegeneration

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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.

Molecular Pharmacology and Pathology of Strokes

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ISBN: 9783038975410 / 9783038975427 Year: Pages: 152 DOI: 10.3390/books978-3-03897-542-7 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General) --- Therapeutics --- Cardiovascular
Added to DOAB on : 2019-02-11 11:33:53
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Stroke, a progressively non-communicable disease, is the second leading cause of death after coronary heart disease in developed countries. The present treatment options for stroke are adapting lifestyle practices, diabetes treatment, drugs, and the management of other factors, but no cure is yet available, despite new insights into molecular and therapeutic targets. Discoveries related to explicating the molecular pharmacology in cerebrovascular function and thrombosis have led to significant advancements in the current treatment paradigm for patients with stroke. Hence, this Special Issue invited scientific papers and reviews from researchers to provide solid evidence from a molecular point of view to scrutinize the molecular pharmacology and pathology of strokes. Platelet activation plays a major role in cardio and cerebrovascular diseases. Platelets also play a key role in the hemostatic process and are associated with various pathological events, such as arterial thrombosis and atherosclerosis. While the currently used anti-platelet drugs such as aspirin and clopidogrel demonstrate efficacy in many patients, they exert undesirable side effects. Therefore, the development of effective therapeutic strategies for the prevention and treatment of thrombotic diseases is a significant priority. Recently, precious metal drugs have conquered the subject of metal-based drugs, and several investigators have moved their attention to the synthesis of various ruthenium (Ru) and iridium (Ir) complexes due to their prospective therapeutic values. We have published this e-book about the “Molecular Pharmacology and Pathology of Strokes” and anticipate that readers will find this book useful regarding the significant challenges and current advances that are presently being made in stroke research, with the possibility of inspiring the application of novel drug development to enrich the devotion and treatment of patients with cardiovascular diseases.

The Physiological Functions of the Amyloid Precursor Protein Gene Family

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453559 Year: Pages: 275 DOI: 10.3389/978-2-88945-355-9 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2018-02-27 16:16:45
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The amyloid precursor protein APP plays a key role in the pathogenesis of Alzheimer’s disease (AD), as proteolytical cleavage of APP gives rise to the Aß peptide which is deposited in the brains of Alzheimer patients. Despite this, our knowledge of the normal cell biological and physiological functions of APP and the closely related APLPs is limited. This may have hampered our understanding of AD, since evidence has accumulated that not only the production of the Aß peptide but also the loss of APP-mediated functions may contribute to AD pathogenesis. Thus, it appears timely and highly relevant to elucidate the functions of the APP gene family from the molecular level to their role in the intact organism, i.e. in the context of nervous system development, synapse formation and adult synapse function, as well as neural homeostasis and aging. Why is our understanding of the APP functions so limited? APP and the APLPs are multifunctional proteins that undergo complex proteolytical processing. They give rise to an almost bewildering array of different fragments that may each subserve specific functions. While Aß is aggregation prone and neurotoxic, the large secreted ectodomain APPsa - produced in the non-amyloidogenic a-secretase pathway - has been shown to be neurotrophic, neuroprotective and relevant for synaptic plasticity, learning and memory. Recently, novel APP cleavage pathways and enzymes have been discovered that have gained much attention not only with respect to AD but also regarding their role in normal brain physiology. In addition to the various cleavage products, there is also solid evidence that APP family proteins mediate important functions as transmembrane cell surface molecules, most notably in synaptic adhesion and cell surface signaling. Elucidating in more detail the molecular mechanisms underlying these divers functions thus calls for an interdisciplinary approach ranging from the structural level to the analysis in model organisms. Thus, in this research topic of Frontiers we compile reviews and original studies, covering our current knowledge of the physiological functions of this intriguing and medically important protein family.

Special Issue Dedicated to Late Professor Takuo Okuda. Tannins and Related Polyphenols Revisited: Chemistry, Biochemistry and Biological Activities

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ISBN: 9783038978343 / 9783038978350 Year: Pages: 316 DOI: 10.3390/books978-3-03897-835-0 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General)
Added to DOAB on : 2019-06-26 10:09:00
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Antioxidative polyphenols represented by tannins and flavonoids are rich in numerous food sources and traditional natural medicines and currently attracting increased attention in health care and food industries because of their multiple biological activities that are favorable to human health. Commemorating the outstanding achievements on tannins by Dr. Takuo Okuda on the occasion of his passing away in December 2016, his colleagues, friends, and worldwide experts of polyphenol research have contributed 18 papers on their recent study to the Special Issue of Molecules. This book is its reprinted form. This covers reviews of structural features, historical usages, and biological activities of unique class of ellagitannins and condensed tannins, and original articles on the most up-to-date findings on the anticancer effect of green tea catechins, the antivirus effect of tannins comparing with the clinically used drugs, the analytical method of ellagitannins using quantitative NMR, the chemical structures of Hydrangea-blue complex (pigment) and condensed tannins in Ephedra sinica and purple prairie clover, and the relationship of condensed tannins in legumes and grape-marc with methane production in the in vitro ruminant system, and others. This book will be useful to natural product chemists and also to researchers in pharmaceutical and/or food industry.

Keywords

Dittrichia viscosa --- antifungal activities --- Candida spp. --- Malassezia spp. --- Microsporum canis --- Aspergillus fumigates --- Ephedra sinica --- proanthocyanidin --- oligomer --- thiolysis --- phloroglucinolysis --- TDDFT --- ECD --- neuraminidase --- inhibition --- tannins --- oseltamivir carboxylate --- zanamivir --- crystal structure --- molecular interactions --- oenothein B --- ellagitannin --- macrocyclic oligomer --- Onagraceae --- Myrtaceae --- Lythraceae --- antioxidants --- antitumor effect --- immunomodulatory effect --- anti-inflammation --- tannin composition --- purple prairie clover --- conservation method --- protein precipitation --- Escherichia coli --- Cynanchum wilfordii --- phenolic glycoside --- 2-O-?-laminaribiosyl-4-hydroxyacetophenone --- cynandione A --- thin layer chromatography --- Cynanchum auriculatum --- Acacia mearnsii bark --- wattle tannin --- proanthocyanidins --- biological activities --- tannins --- vegetable tanning --- European historic leathers --- colorimetric tests --- spectroscopy --- UV-Vis --- FTIR --- triple-negative breast cancer --- fatty acid synthase --- FASN inhibition --- polyphenolic FASN inhibitors --- (?)-epigallocatechin 3-gallate --- synthetic analogues --- apoptosis --- anticancer activity --- 1H-NMR --- quantitative NMR --- ellagitannin --- Geranium thunbergii --- geraniin --- Aluminum ion --- blue color development --- 5-O-caffeoylquinic acid --- 3-O-glucosyldelphinidin --- Hydrangea macrophylla --- ESI-mass --- metal complex --- Coreopsis lanceolata L. --- chalcone --- flavanone --- flavonol --- aurone --- Horner–Wadsworth–Emmons reaction --- condensed tannin --- bioactivity --- methanogenesis --- grape marc --- fatty acids --- in vitro batch fermentation --- neuroprotection --- PC12 --- NGF --- differentiation --- amyloid-? peptide --- taxanes --- hormesis --- polyphenol --- bamboo leaf extract --- overlay method --- ellagitannin --- structure --- revision --- (?)-epigallocatechin gallate --- immune checkpoint --- interferon-? --- epidermal growth factor --- lung tumor --- proanthocyanidins --- condensed tannins --- thiolysis --- NMR spectroscopy --- ultrahigh-resolution negative mode MALDI-TOF mass spectrometry --- antioxidant --- ORAC assay --- Acacia --- forage legume --- Trapa taiwanensis Nakai --- hydrolysable tannin --- stability --- gallotannin --- ellagitannin

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