Search results: Found 22

Listing 1 - 10 of 22 << page
of 3
>>
Sort by
Innate immunity and neurodegenerative disorders

Authors: ---
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
License:

Loading...
Export citation

Choose an application

Abstract

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.

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

Authors: ---
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
License:

Loading...
Export citation

Choose an application

Abstract

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.

Tau oligomers

Authors: ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192618 Year: Pages: 113 DOI: 10.3389/978-2-88919-261-8 Language: English
Publisher: Frontiers Media SA
Subject: Psychiatry --- Neurology --- Medicine (General) --- Science (General)
Added to DOAB on : 2015-12-03 13:02:24
License:

Loading...
Export citation

Choose an application

Abstract

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

Neuronal Self-Defense: Compensatory Mechanisms in Neurodegenerative Disorders

Authors: ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197590 Year: Pages: 190 DOI: 10.3389/978-2-88919-759-0 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
License:

Loading...
Export citation

Choose an application

Abstract

Neurodegenerative disorders are characterized by the progressive loss of specific populations of neurons with consequent deterioration of brain's function and dramatic impact on human behavior. At present, there are no effective cures for neurodegenerative diseases. Because unambiguous diagnosis is possible only after manifestation of symptoms, when a large proportion of neurons has been already lost, therapies are necessarily confined to alleviation of symptoms. Development of cures halting the disease course is hampered by our rudimentary understanding of the etiopathology. Most neurodegenerative disorders are sporadic and age-related and - even for those of known genetic origin - the mechanisms influencing disease onset and progression have not been fully characterized. The different diseases, however, share important similarities in the mechanisms responsible for neuronal loss, which is caused by a combination of endogenous and exogenous challenges. Trophic deprivation, oxidative stress, accumulation of abnormal protein aggregates, and bioenergetics defects have been described in most, if not all, neurodegenerative disease. To counterbalance these noxious stimuli cells deploy, at least during the initial pathogenic states, intrinsic neuroprotective responses. These are general compensatory mechanisms, common to several neurodegenerative conditions, which reprogram cellular physiology to overcome stress. Adaptation includes strategies to optimize energetic resources, for instance reduction of rRNA synthesis to repress translation, suppression of transcription, and bioenergetics and metabolic redesign. Additional mechanisms include potentiation of antioxidant capacity, induction of endoplasmic reticulum (ER) stress, and activation of protein quality control systems and autophagy. Ineffective execution of these compensatory strategies severely threatens cellular homeostasis and favors onset of pathology. Therefore, a better understanding of these "buffering" mechanisms and of their interconnections may help to devise more effective therapeutic tools to prolong neuronal survival and activity, independently of the original genetic mutations and stress insults. This Research Topic focuses on the initial compensatory responses protecting against failure of those mechanisms that sustain neuronal survival and activity. The collection intends to summarize the state-of-the-art in this field and to propose novel research contributes, with the ultimate goal of inspiring innovative studies aimed to contrast progression of neurodegenerative diseases.

Nicotinic Acetylcholine Receptor Signaling in Neuroprotection

Authors: --- ---
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
License:

Loading...
Export citation

Choose an application

Abstract

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.

Clinical use of biomarkers in neurodegenerative disorders

Author:
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
License:

Loading...
Export citation

Choose an application

Abstract

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.

Metals and neurodegeneration: Restoring the balance

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197392 Year: Pages: 132 DOI: 10.3389/978-2-88919-739-2 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
License:

Loading...
Export citation

Choose an application

Abstract

Biometals such as copper, zinc and iron have key biological functions, however, aberrant metabolism can lead to detrimental effects on cell function and survival. These biometals have important roles in the brain, driving cellular respiration, antioxidant activity, intracellular signaling and many additional structural and enzymatic functions. There is now considerable evidence that abnormal biometal homeostasis is a key feature of many neurodegenerative diseases and may have an important role in the onset and progression of disorders such as Alzheimer’s, Parkinson’s, prion and motor neuron diseases. Recent studies also support biometal roles in a number of less common neurodegenerative disorders. The role of biometals in a growing list of brain disorders is supported by evidence from a wide range of sources including molecular genetics, biochemical studies and biometal imaging. These studies have spurred a growing interest in understanding the role of biometals in brain function and disease as well as the development of therapeutic approaches that may be able to restore the altered biometal chemistry of the brain. These approaches range from genetic manipulation of biometal transport to chelation of excess metals or delivery of metals where levels are deficient. A number of these approaches are offering promising results in cellular and animal models of neurodegeneration with successful translation to pre-clinical and clinical trials. At a time of aging populations and slow progress in development of neurotherapeutics to treat age-related neurodegenerative diseases, there is now a critical need to further our understanding of biometals in neurodegeneration. This issue covers a broad range of topics related to biometals and their role in neurodegeneration. It is hoped that this will inspire greater discussion and exchange of ideas in this crucial area of research and lead to positive outcomes for sufferers of these neurodegenerative diseases.

Molecular Diagnostics in the Detection of Neurodegenerative Disorders

Authors: ---
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
License:

Loading...
Export citation

Choose an application

Abstract

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.

Ubiquitin and the Brain: Roles of Proteolysis in the Normal and Abnormal Nervous System

Authors: ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452859 Year: Pages: 241 DOI: 10.3389/978-2-88945-285-9 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2018-02-27 16:16:44
License:

Loading...
Export citation

Choose an application

Abstract

Proteolysis by the ubiquitin-proteasome pathway (UPP) in the nervous system has been extensively studied both in the context of normal physiological function as well as abnormal pathological conditions. Although ubiquitin was used as a marker of brain pathology, the normal functions of the UPP were not studied much in the nervous system until the 1990s. The early investigations focused on synaptic plasticity which was followed by studies on the roles of protein degradation in the development of the nervous system. Research on the role of abnormal roles of the UPP follows a parallel trajectory. Since the 2000s, the field has grown to encompass many subareas of research and several model systems. Despite the progress made, many unanswered questions still remain. For example, there are many unknowns about the precise spatial and temporal control of protein degradation in the normal nervous system. With respect to the roles of proteolysis in brain pathology a major challenge is to elucidate the connection between impaired protein degradation and disease progression. In addition, in-depth studies of the roles of ubiquitin-proteasome-mediated proteolysis in neurodegenerative diseases are promising in identifying therapeutic targets. This ebook contains original research papers and insightful reviews that cover several aspects of proteolysis by the UPP and its physiological as well as pathological functions in the nervous system.

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

Authors: --- --- --- --- et al.
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
License:

Loading...
Export citation

Choose an application

Abstract

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.

Listing 1 - 10 of 22 << page
of 3
>>
Sort by
Narrow your search