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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.

Basal ganglia: physiological, behavioral, and computational studies

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193882 Year: Pages: 494 DOI: 10.3389/978-2-88919-388-2 Language: English
Publisher: Frontiers Media SA
Subject: Science (General)
Added to DOAB on : 2015-12-03 13:02:24
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The basal ganglia has received much attention over the last two decades, as it has been implicated in many neurological and psychiatric disorders. Most of this research - in both animals and humans - attempt to understand the neural and biochemical substrates of basic motor and learning processes, and how these are affected in human patients as well as animal models of brain disorders. The current volume contains research articles and reviews describing basic, pre-clinical and clinical neuroscience research of the basal ganglia written by attendees of the 11th Triennial Meeting of the International Basal Ganglia Society (IBAGS) that was held March 3-7th, 2013 at the Princess Hotel, Eilat, Israel and by researchers of the basal ganglia. Specifically, articles in this volume include research reports on the biochemistry, computational theory, anatomy and physiology of single neurons and functional circuitry of the basal ganglia networks as well as the latest data on animal models of basal ganglia dysfunction and clinical studies in human patients.

Parkinson's Disease Cell Vulnerability and Disease Progression

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196760 Year: Pages: 194 DOI: 10.3389/978-2-88919-676-0 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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Parkinson's disease is a neurodegenerative disorder that affects 1.5% of the global population over 65 years of age. The hallmark feature of this disease is the degeneration of dopamine neurons in the substantia nigra pars compacta and a consequent striatal dopamine deficiency. The pathogenesis of Parkinson's Disease remains unclear. Despite tremendous growth in recent years in our knowledge of the molecular basis of Parkinson's Disease and the molecular pathways of cell death important questions remain regarding why are substantia nigra cells especially vulnerable, which mechanisms underlie progressive cell loss or what do Lewy bodies or alpha-synuclein reveal about disease progression. Understanding the different vulnerability of the dopaminergic neurons from midbrain regions and the mechanisms whereby pathology becomes widespread are primary objectives of basic and clinical research in Parkinson's Disease.This e-Book discusses the etiopathogenesis of Parkinson's Disease, presenting a series of papers that provide up-to-date, state-of-the-art information on molecular and cellular mechanisms involved in the neurodegeneration process in the disease, the role of activation of functional anatomical organization of the basal ganglia and in particular habitual vs goal directed systems as a factor of neuronal vulnerability, the possibility that Parkinson's Disease coulb be a prion disease and how genetic factors linked to familial and sporadic forms of PD. We hope that this e-Book will stimulate the continuing efforts to understand the cell and physiological mechanisms underlying the origin of Parkinson's Disease.

Biology of Cognitive Aging: Model Systems, Technologies and Beyond

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451449 Year: Pages: 145 DOI: 10.3389/978-2-88945-144-9 Language: English
Publisher: Frontiers Media SA
Subject: Genetics --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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Welcome! We, humans, tend to experience forgetfulness when we get old. The forgetfulness may become more serious memory impairment, dementia. Presumably, we have known it for a long time, but we still do not know the mechanism behind. A normal part of forgetfulness is called age-related memory impairment (AMI), which is considered the first step towards mild cognitive impairment (MCI; transition state) and dementia (disease state). The majority of dementia is attributable to Alzheimer’s disease (AD). Progression to dementia occurs at a high rate in patients with AMI. This eBook covers exciting but yet challenging field of cognitive aging. AMI is specific to neural tissues of the brain and is considered to be segmental aging. It happens not only to humans but also to a variety of species. Learning and memory are vulnerable to aging in a wide variety of model species, including worms, fruit flies, insects, snails, fishes, and rodents. Aging specifically reduces the ability to learn new information but leaves “old” memories and procedural memory intact. A comparative approach including the use of model systems seems to facilitate understanding of the molecular mechanisms that lead to AMI and AD. We advocate research on model systems. This eBook also provides the first manuscript co-authored with an AD patient to create a feedback loop from patients incorporated into research. We also included a manuscript on the semi-automated system that was inspired by such a feedback. Those may place a nice flavor to this exciting series of comparative research on cognitive aging. We hope you enjoy this eBook. Warm regards, Shin Murakami, Ph.D.Welcome! We, humans, tend to experience forgetfulness when we get old. The forgetfulness may become more serious memory impairment, dementia. Presumably, we have known it for a long time, but we still do not know the mechanism behind. A normal part of forgetfulness is called age-related memory impairment (AMI), which is considered the first step towards mild cognitive impairment (MCI; transition state) and dementia (disease state). The majority of dementia is attributable to Alzheimer’s disease (AD). Progression to dementia occurs at a high rate in patients with AMI. This eBook covers exciting but yet challenging field of cognitive aging. AMI is specific to neural tissues of the brain and is considered to be segmental aging. It happens not only to humans but also to a variety of species. Learning and memory are vulnerable to aging in a wide variety of model species, including worms, fruit flies, insects, snails, fishes, and rodents. Aging specifically reduces the ability to learn new information but leaves “old” memories and procedural memory intact. A comparative approach including the use of model systems seems to facilitate understanding of the molecular mechanisms that lead to AMI and AD. We advocate research on model systems. This eBook also provides the first manuscript co-authored with an AD patient to create a feedback loop from patients incorporated into research. We also included a manuscript on the semi-automated system that was inspired by such a feedback. Those may place a nice flavor to this exciting series of comparative research on cognitive aging. We hope you enjoy this eBook. Warm regards, Shin Murakami, Ph.D.

Neurodegeneration: From Genetics to Molecules

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450206 Year: Pages: 264 DOI: 10.3389/978-2-88945-020-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2018-02-27 16:16:44
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Chronic degenerative diseases are one of the major public health problems, particularly those affecting the nervous system. They are characterized by the degeneration of specific cell populations that include several pathologies which contribute significantly to morbidity and mortality in the elderly population. Therefore, in recent years, the study of neuroscience has gained significant importance. Most of these neurodegenerative disorders are the result of a complex interaction between genetic and environmental factors that generate progression and can even determine its severity. The presence of mutations in genes as LRRK2, SNCA, PARK7, PARK2 or PINK1 is associated with Parkinson's disease. Mutations in genes such as APP, PS1 and PS2 are associated with familial Alzheimer's disease; while HTT gene mutations are the cause of Huntington's disease. In most cases, this condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. It is known that these mutations can also alter the proteins function; however, it has not yet been possible to fully understand how some genetic changes cause the disease or influence the risk of developing these disorders. Most symptoms seen in these conditions occurs when specific nerve cells are damaged or die generating a loss in brain communication. Also many of these mutations generate aggregation of intracellular or extracellular proteins affecting cell function and eventually causing neuronal death. It is unclear whether the presence of these aggregates play an important role in nerve cell death during the development of neurodegenerative diseases, or if they are simply part of the response of cells to the disease. Other mutations affect the mitochondrial function generating alterations in energy production and promoting the formation of unstable molecules such as free radicals. Under normal conditions, the harmful effects caused by free radicals, are offset within the cell. However, in pathological conditions, the presence of mutations can alter this process by allowing the accumulation of radicals and damaging or killing cells. On the other hand, we also know that these diseases may not have a direct genetic component, thus, the study of sporadic type neurodegenerative diseases is much more complex. Histopathological lesions as well as the cellular and molecular alterations are generally indistinguishable from familial cases. For this reason, it is important to understand the genetic and molecular mechanisms associated with this type of pathologies. In this sense, this issue aims to understand the molecular processes that occur in the brain, and how these are influenced by the environment, genetics and behavior.

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.

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.

Genome Editing in Neurosciences

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Book Series: Research and Perspectives in Neurosciences ISSN: 0945-6082 / 2196-3096 ISBN: 9783319601915 9783319601922 Year: Pages: 123 DOI: https://doi.org/10.1007/978-3-319-60192-2 Language: English
Publisher: Springer
Subject: Neurology --- Genetics
Added to DOAB on : 2017-11-24 13:07:59
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Innovations in molecular biology are allowing neuroscientists to study the brain with unprecedented resolution, from the level of single molecules to integrated gene circuits. Chief among these innovations is the CRISPR-Cas genome editing technology, which has the precision and scalability to tackle the complexity of the brain. This Colloque Médecine et Recherche has brought together experts from around the world that are applying genome editing to address important challenges in neuroscience, including basic biology in model organisms that has the power to reveal systems-level insight into how the nervous system develops and functions as well as research focused on understanding and treating human neurological disorders.

New Advanced Wireless Technologies for Objective Monitoring of Motor Symptoms in Parkinson's Disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454860 Year: Pages: 122 DOI: 10.3389/978-2-88945-486-0 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Neurology
Added to DOAB on : 2019-01-23 14:53:42
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Over the last decade, a growing number of researchers have used advanced wireless technologies including wearable sensors for objective evaluation of specific motor symptoms in patients with Parkinson's disease (PD). In the near future, sensing technologies will likely provide relevant advances in the clinical management of patients with PD, contributing to early diagnosis, disease progression monitoring and therapeutic approach. In this regard, this eBook hosts new original studies focused on the objective monitoring of motor symptoms and therapeutic perspectives of wireless technologies in patients with PD.

Sound, Music and Movement in Parkinson's Disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450794 Year: Pages: 176 DOI: 10.3389/978-2-88945-079-4 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Neurology --- Science (General) --- Psychology
Added to DOAB on : 2017-07-06 13:27:36
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Recent years have brought new insights to the understanding of Parkinson’s disease, impact of exercise and sound displays in rehabilitation and movement facilitation. There is growing evidence that auditory signals in the environment can provide a temporal template for movement and change the mode of motor control from intrinsic to extrinsic; habitual to goal-directed, enabling enhanced motor performance in patients. In addition, forced exercise rate studies show that exercising at the pace of healthy adults can have potential neuroprotective benefits for patients. Many research groups have explored the use of auditory cues (such as rhythmical auditory training) in improving gait and upper limb movement parameters. Cues are usually either intermittent (metronome) or continuous (dynamic sound displays). Similarly, dance based interventions suggest that patients benefit from additional sensory information (i.e. the temporal structure embedded in music and proprioceptive information from a dancing partner) that facilities movement. On the contrary, studies dedicated to auditory perception and motor timing report an impaired ability of patients to perceive and synchronise with complex rhythmical structures (i.e. causing an inability to play musical instruments). With the growth of modern technology and the increasing portability of hi-specification devices (such as smart phones), new research questions on the design of interventions are beginning to emerge as we strive for more efficient therapeutic approaches. In this Research Topic we wanted to bring together top scientists from the movement disorder, motor control and sound related studies along with therapists. That way, we can engage in cross-disciplinary and challenging scientific debate about future rehabilitation avenues and frontiers for Parkinson’s disease patients.

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