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Cellular and molecular mechanisms of motor neuron death in amyotrophic lateral sclerosis

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193769 Year: Pages: 190 DOI: 10.3389/978-2-88919-376-9 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-11-19 16:29:12
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Amyotrophic lateral sclerosis (ALS), which was described since 1869 by Jean Martin Charcot, is a devastating neurodegenerative disease characterized by the selective and progressive loss of upper and lower motor neurons of the cerebral cortex, brainstem and the spinal cord. The cognitive process is not affected and is not merely the result of aging because may occur at young ages. The only known cause of the disease is associated with genetic mutations, mainly in the gene encoding superoxide dismutase 1 (familial ALS), whereas there is no known cause of the sporadic form of ALS (SALS), which comprises >90% of cases. Both ALS types develop similar histopathological and clinical characteristics, and there is no treatment or prevention of the disease. Because effective treatments for ALS, as for other neurodegenerative diseases, can only result from the knowledge of their cellular and molecular pathophysiological mechanisms, research on such mechanisms is essential. Although progress in neurochemical, physiological and clinical investigations in the last decades has identified several mechanisms that seem to be involved in the cell death process, such as glutamate-mediated excitotoxicity, alterations of inhibitory circuits, inflammatory events, axonal transport deficits, oxidative stress, mitochondrial dysfunction and energy failure, the understanding of the origin and temporal progress of the disease is still incomplete and insufficient. Clearly, there is a need of further experimental models and approaches to discern the importance of such mechanisms and to discover the factors that determine the selective death of motor neurons characteristic of ALS, in contrast to other neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. Whereas studies in vitro in cell cultures, tissue slices or organotypic preparations can give useful information regarding cellular and molecular mechanisms, the experiments in living animal models obviously reflect more closely the situation in the human disease, provided that the symptoms and their development during time mimics as close as possible those of the human disease. It is necessary to correlate the experimental findings in vitro with those in vivo, as well as those obtained in genetic models with those in non-genetic models, aiming at designing and testing therapeutic strategies based on the results obtained.

Psychological Issues in Amyotrophic Lateral Sclerosis

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197583 Year: Pages: 103 DOI: 10.3389/978-2-88919-758-3 Language: English
Publisher: Frontiers Media SA
Subject: Psychology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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Amyotrophic lateral sclerosis is a fatal and progressive disease, characterized by progressive muscles weakness, with consequent loss of physical capacities. Patients become relentlessly immobile and, in the late stages of the disease, develop a "locked-in" state in which only residual muscular movement is possible, but the intellect and the personality usually remain unimpaired. At now, there is no cure for ALS. The psychological impact of the disease is huge, on both patients and caregivers. Aim of the present Research Topic is to collect new evidence about quality of life, depression, anxiety, pain, spiritual and existential issues, hope and hopelessness in the ALS field, with attention to both patients and their caregivers. Emphasis will be provided to the investigation of psychological support and the possible role of psychologists in this challenging field. Keywords: Amyotrophic Lateral Sclerosis; Health Psychology; Clinical Psychology, Motor Neuron Disorder; Quality of Life. Subtopics:The subtopics to be covered in the Research Topic include, but not limited to:1. Assessment of psychological variables in ALS2. Quality of life during the course of the illness3. Impact of technological assistance to illness (wheelchairs, NIV...)4. Interfaces among biological, psychosocial, and social factors5. Psychological and psychotherapeutic interventions6. Couple and family relationships7. Research methodology, measurement and statistics8. Cultural and social features of ALS9. Professional issues, including training and supervision10. Implications of research findings for health-related policy

Neuroimmune Interface in Health and Diseases

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453788 Year: Pages: 174 DOI: 10.3389/978-2-88945-378-8 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology --- Neurology
Added to DOAB on : 2018-11-16 17:17:57
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It is now well appreciated that the immune system, in addition to its traditional role in defending the organism against pathogens, communicate in a well-organized fashion with the brain to maintain homeostasis and regulate a set of neural functions. Perturbation in this brain-immune interactions due to inflammatory responses may lead to psychiatric and neurological disorders. Microglia are one of the essential cells involved in the brain-immune interactions. Microglial cells are now not simply regarded as resident tissue macrophages in the brain. These cells are derived from myeloid progenitor cells in the yolk sac in early gestation, travel to the brain parenchyma and interact actively with neurons during the critical period of neurogenesis. Microglia provide a trophic support to developing neurons and take part in the neural wiring through the activity-dependent synapse elimination via direct neuron-microglia interactions. Altered microglial functions including changes in the gene expression due to early life inflammatory events or psychological and environmental stressors can be causally related to neurodevelopmental diseases and mental health disorders. This type of alterations in the neural functions can occur in the absence of infiltration of inflammatory cells in the brain parenchyma or leptomeninges. In this sense, the pathogenetic state underlying a significant part of psychiatric and neurological diseases may be similar to “para-inflammation”, an intermediate state between homeostatic and classical inflammatory states as defined by Ruslan Medzhitov (Nature 454:428-35, 2008). Therefore, it is important to study how systemic inflammation affects brain health and how local peripheral inflammation induces changes in the brain microenvironment. Chronic pain is also induced by disturbance in otherwise well-organized multisystem interplay comprising of reciprocal neural, endocrine and immune interactions. Especially, early-life insults including exposure to immune challenges can alter the neuroanatomical components of nociception, which induces altered pain response later in life. Recently the discrete roles of microglia and blood monocyte-derived macrophages are being defined. The distinction may be further highlighted by disorders in which the brain parenchymal tissue is damaged. Therefore, studies investigating the dynamics of immune cells in traumatic brain injury and neurotropic viral infections including human immunodeficiency virus, etc. as well as neurodegenerative diseases such as amyotrophic lateral sclerosis are promising to clarify the interplay between the central nervous and immune systems. The understanding of the histological architecture providing the infrastructure of such neuro-immune interplay is also essential. This Frontiers research topic brings together fourteen articles and aims to create a platform for researchers in the field of psychoneuroimmunology to share the recent theories, hypotheses and future perspectives regarding open questions on the mechanisms of cell-cell interactions with chemical mediators among the nervous, immune and endocrine systems. We hope that this platform would reveal the relevance of the studies on multisystem interactions to enhance the understanding of the mechanisms underlying a wide variety of neurological and psychiatric disorders.

The molecular pathology of cognitive decline: Focus on metals

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197200 Year: Pages: 175 DOI: 10.3389/978-2-88919-720-0 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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In the past two decades there have been significant advances made in understanding the cellular and molecular alterations that occur with brain ageing, as well as with our understanding of age-related brain diseases. Ageing is associated with a mid-life decline in many cognitive domains (eg. Attention, working memory, episodic memory) that progresses with advancing age and which may be potentiated by a variety of diseases. However, despite the breadth of attempts to explain it, the underlying basis for age-related memory impairment remains poorly understood. Both normal and “pathological” ageing (as in age-related neurodegenerative disorders such as Alzheimer’s disease) may be associated with overlapping and increased levels of “abnormal” pathology, and this may be a potential mediator of cognitive decline in both populations. An emerging hypothesis in this field is that metal ion dys/homeostasis may represent a primary unifying mechanism to explain age- and disease-associated memory impairment – either indirectly via an effect on disease pathogenesis, or by a direct effect on signaling pathways relevant to learning and memory. There remains a concerted worldwide effort to deliver an effective therapeutic treatment for cognitive decline associated with ageing and/or disease, which is currently an unmet need. There have been numerous clinical trials conducted specifically testing drugs to prevent cognitive decline and progression to dementia, but to date the results have been less than impressive, highlighting the urgent need for a greater understanding of the neurobiological basis of memory impairment in ageing and disease which can then drive the search for effective therapeutics.

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.

The Role of Mitochondria, Oxidative Stress and Altered Calcium Homeostasis in Amyotrophic Lateral Sclerosis: From Current Developments in the Laboratory to Clinical Treatments

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451463 Year: Pages: 336 DOI: 10.3389/978-2-88945-146-3 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, devastating and fatal disease characterized by selective loss of upper and lower motor neurons of the cerebral cortex, brainstem, spinal cord and muscle atrophy. In spite of many years of research, the pathogenesis of ALS is still not well understood. ALS is a multifaceted genetic disease, in which genetic susceptibility to motor neuron death interacts with environmental factors and there is still no cure for this deleterious disease. At present, there is only one FDA approved drug, Riluzole which according to past studies only modestly slows the progression of the disease, and improves survival by up to three months. The suffering of the ALS patients, and their families is enormous and the economic burden is colossal. There is therefore a pressing need for new therapies. Different molecular pathways and pathological mechanisms have been implicated in ALS. According to past studies, altered calcium homeostasis, abnormal mitochondrial function, protein misfolding, axonal transport defects, excessive production of extracellular superoxide radicals, glutamate-mediated excitotoxicity, inflammatory events, and activation of oxidative stress pathways within the mitochondria and endoplasmic reticulum can act as major contributor that eventually leads to loss of connection between muscle and nerve ultimately resulting to ALS. However, the detailed molecular and cellular pathophysiological mechanisms and origin and temporal progression of the disease still remained elusive. Ongoing research and future advances will likely advance our improve understanding about various involved pathological mechanism ultimately leading to discoveries of new therapeutic cures. Importantly, clinical biomarkers of disease onset and progression are thus also urgently needed to support the development of the new therapeutic agents and novel preventive and curative strategies. Effective translation from pre-clinical to clinical studies will further require extensive knowledge regarding drug activity, bioavailability and efficacy in both the pre-clinical and clinical setting, and proof of biological activity in the target tissue. During the last decades, the development of new therapeutic molecules, advance neuroimaging tools, patient derived induced stem cells and new precision medicine approaches to study ALS has significantly improved our understanding of disease. In particular, new genetic tools, neuroimaging methods, cellular probes, biomarker study and molecular techniques that achieve high spatiotemporal resolution have revealed new details about the disease onset and its progression. In our effort to provide the interested reader, clinician and researchers a comprehensive summaries and new findings in this field of ALS research, hereby we have created this electronic book which comprises of twenty seven chapters having various reviews, perspective and original research articles. All these chapters and articles in this book not only summarize the cutting-edge techniques, approaches, cell and animal models to study ALS but also provide unprecedented coverage of the current developments and new hypothesis emerging in ALS research. Some examples are novel genetic and cell culture based models, mitochondria-mediated therapy, oxidative stress and ROS mechanism, development of stem cells and mechanism-based therapies as well as novel biomarkers for designing and testing effective therapeutic strategies that can benefit ALS patients who are at the earlier stages in the disease. I am extremely grateful to all the contributors to this book and want to thank them for their phenomenal efforts. Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, devastating and fatal disease characterized by selective loss of upper and lower motor neurons of the cerebral cortex, brainstem, spinal cord and muscle atrophy. In spite of many years of research, the pathogenesis of ALS is still not well understood. ALS is a multifaceted genetic disease, in which genetic susceptibility to motor neuron death interacts with environmental factors and there is still no cure for this deleterious disease. At present, there is only one FDA approved drug, Riluzole which according to past studies only modestly slows the progression of the disease, and improves survival by up to three months. The suffering of the ALS patients, and their families is enormous and the economic burden is colossal. There is therefore a pressing need for new therapies. Different molecular pathways and pathological mechanisms have been implicated in ALS. According to past studies, altered calcium homeostasis, abnormal mitochondrial function, protein misfolding, axonal transport defects, excessive production of extracellular superoxide radicals, glutamate-mediated excitotoxicity, inflammatory events, and activation of oxidative stress pathways within the mitochondria and endoplasmic reticulum can act as major contributor that eventually leads to loss of connection between muscle and nerve ultimately resulting to ALS. However, the detailed molecular and cellular pathophysiological mechanisms and origin and temporal progression of the disease still remained elusive. Ongoing research and future advances will likely advance our improve understanding about various involved pathological mechanism ultimately leading to discoveries of new therapeutic cures. Importantly, clinical biomarkers of disease onset and progression are thus also urgently needed to support the development of the new therapeutic agents and novel preventive and curative strategies. Effective translation from pre-clinical to clinical studies will further require extensive knowledge regarding drug activity, bioavailability and efficacy in both the pre-clinical and clinical setting, and proof of biological activity in the target tissue. During the last decades, the development of new therapeutic molecules, advance neuroimaging tools, patient derived induced stem cells and new precision medicine approaches to study ALS has significantly improved our understanding of disease. In particular, new genetic tools, neuroimaging methods, cellular probes, biomarker study and molecular techniques that achieve high spatiotemporal resolution have revealed new details about the disease onset and its progression. In our effort to provide the interested reader, clinician and researchers a comprehensive summaries and new findings in this field of ALS research, hereby we have created this electronic book which comprises of twenty seven chapters having various reviews, perspective and original research articles. All these chapters and articles in this book not only summarize the cutting-edge techniques, approaches, cell and animal models to study ALS but also provide unprecedented coverage of the current developments and new hypothesis emerging in ALS research. Some examples are novel genetic and cell culture based models, mitochondria-mediated therapy, oxidative stress and ROS mechanism, development of stem cells and mechanism-based therapies as well as novel biomarkers for designing and testing effective therapeutic strategies that can benefit ALS patients who are at the earlier stages in the disease. I am extremely grateful to all the contributors to this book and want to thank them for their phenomenal efforts.

Molecular, Cellular and Model Organism Approaches for Understanding the Basis of Neurological Disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451739 Year: Pages: 183 DOI: 10.3389/978-2-88945-173-9 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2017-08-28 14:01:09
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The advent of next-generation sequencing technologies has resulted in a remarkable increase our understanding of human and animal neurological disorders through the identification of disease causing or protective sequence variants. However, in many cases, robust disease models are required to understand how changes at the DNA, RNA or protein level affect neuronal and synaptic function, or key signalling pathways. In turn, these models may enable understanding of key disease processes and the identification of new targets for the medicines of the future. This e-book contains original research papers and reviews that highlight either the impact of next-generation sequencing in the understanding of neurological disorders, or utilise molecular, cellular, and whole-organism models to validate disease-causing or protective sequence variants.

Regulatory microRNA

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ISBN: 9783038977681 9783038977698 Year: Pages: 348 DOI: 10.3390/books978-3-03897-769-8 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Genetics
Added to DOAB on : 2019-04-25 16:37:17
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This book includes updated information about microRNA regulation, for example, in the fields of circular RNAs, multiomics analysis, biomarkers and oncogenes. The variety of topics included in this book reaffirms the extent to which microRNA regulation affects biological processes. Although microRNAs are not translated to proteins, their importance for biological processes is not less than proteins. An understanding of their roles in various biological processes is critical to understanding gene function in these biological processes. Although non-coding RNAs other than microRNAs have recently come under investigation, microRNA still remains the front runner as the subject of genetic and biological studies. In reading the collection of papers, readers can grasp the most updated information regarding microRNA regulation, which will continue to be an important topic in genetics and biology.

Keywords

tensor decomposition --- miRNA transfection --- sequence-nonspecific off-target regulation --- extracellular vesicles --- cancer --- therapeutics --- miRNA --- virus --- host --- Cross-Kingdom --- target prediction --- microRNAs --- autophagy --- mitophagy --- cardiac diseases --- biomarker --- calf --- Ileum --- miRNA-mRNA integration --- miRNA sequencing --- growth --- development --- microRNA --- myelodysplastic syndromes --- acute myeloid leukemia --- azacitidine --- 14q32 --- MEG3 --- autophagy regulator --- transcriptional factor --- non-coding RNA --- regulatory network --- RWR algorithm --- circular RNA --- circFGFR2 --- FGFR2 --- miR-133a-5p --- miR-29b-1-5p --- skeletal muscle --- proliferation --- differentiation --- breast cancer --- CAFs --- estrogens --- GPER --- miR-338-3p --- c-Fos --- Cyclin D1 --- amyotrophic lateral sclerosis (ALS) --- biomarker --- microRNA --- cerebrospinal fluid (CSF) --- muscle biopsy --- circulating miRNAs --- RNA interference --- small interfering RNA --- microRNA --- oncolytic virotherapy --- conditionally replicating adenovirus (CRAd) --- biomarker --- gene --- microRNA --- parkinson’s disease --- miRNA --- bioinformatic analysis --- ischemic stroke --- miRNA-gene target interaction --- network --- biomarker --- diagnosis --- prognosis --- microRNAs --- epigenetic biomarker --- sepsis --- inflammation --- Teleostei --- embryogenesis --- tissue-enriched miRNAs --- post-transcriptional gene regulation --- miRNA expression and regulation --- passenger miRNA --- biomarker --- vascular injury --- smooth muscle cells --- porcine vein graft and stent models --- bone angiogenesis --- osteogenesis --- angiogenic-osteogenic coupling --- microRNAs --- bone regeneration --- bone formation --- bone tissue-engineering --- angiomiRs --- osteomiRs --- hypoxamiRs --- circular RNA --- circHIPK3 --- microRNA --- miR-30a-3p --- skeletal muscle --- proliferation --- differentiation

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