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Intellectual Disabilities in Down Syndrome from Birth and throughout Life: Assessment and Treatment

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450459 Year: Pages: 179 DOI: 10.3389/978-2-88945-045-9 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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Research on the multiple aspects of cognitive impairment in Down syndrome (DS), from genes to behavior to treatment, has made tremendous progress in the last decade. The study of congenital intellectual disabilities such as DS is challenging since they originate from the earliest stages of development and both the acquisition of cognitive skills and neurodegenerative pathologies are cumulative. Comorbidities such as cardiac malformations, sleep apnea, diabetes and dementia are frequent in the DS population, as well, and their increased risk provides a means of assessing early stages of these pathologies that is relevant to the general population. Notably, persons with DS will develop the histopathology of Alzheimer’s disease (formation of neuritic plaques and tangles) and are at high risk for dementia, something that cannot be predicted in the population at large. Identification of the gene encoding the amyloid precursor protein, its localization to chromosome 21 in the 90’s and realization that all persons with DS develop pathology identified this as an important piece of the amyloid cascade hypothesis in Alzheimer’s disease. Awareness of the potential role of people with DS in understanding progression and treatment as well as identification of genetic risk factors and also protective factors for AD is reawakening. For the first time since DS was recognized, major pharmaceutical companies have entered the search for ameliorative treatments, and phase II clinical trials to improve learning and memory are in progress. Enriched environment, brain stimulation and alternative therapies are being tested while clinical assessment is improving, thus increasing the chances of success for therapeutic interventions. Researchers and clinicians are actively pursuing the possibility of prenatal treatments for many conditions, an area with a huge potential impact for developmental disorders such as DS. Our goal here is to present an overview of recent advances with an emphasis on behavioral and cognitive deficits and how these issues change through life in DS. The relevance of comorbidities to the end phenotypes described and relevance of pharmacological targets and possible treatments will be considerations throughout.Research on the multiple aspects of cognitive impairment in Down syndrome (DS), from genes to behavior to treatment, has made tremendous progress in the last decade. The study of congenital intellectual disabilities such as DS is challenging since they originate from the earliest stages of development and both the acquisition of cognitive skills and neurodegenerative pathologies are cumulative. Comorbidities such as cardiac malformations, sleep apnea, diabetes and dementia are frequent in the DS population, as well, and their increased risk provides a means of assessing early stages of these pathologies that is relevant to the general population. Notably, persons with DS will develop the histopathology of Alzheimer’s disease (formation of neuritic plaques and tangles) and are at high risk for dementia, something that cannot be predicted in the population at large. Identification of the gene encoding the amyloid precursor protein, its localization to chromosome 21 in the 90’s and realization that all persons with DS develop pathology identified this as an important piece of the amyloid cascade hypothesis in Alzheimer’s disease. Awareness of the potential role of people with DS in understanding progression and treatment as well as identification of genetic risk factors and also protective factors for AD is reawakening. For the first time since DS was recognized, major pharmaceutical companies have entered the search for ameliorative treatments, and phase II clinical trials to improve learning and memory are in progress. Enriched environment, brain stimulation and alternative therapies are being tested while clinical assessment is improving, thus increasing the chances of success for therapeutic interventions. Researchers and clinicians are actively pursuing the possibility of prenatal treatments for many conditions, an area with a huge potential impact for developmental disorders such as DS. Our goal here is to present an overview of recent advances with an emphasis on behavioral and cognitive deficits and how these issues change through life in DS. The relevance of comorbidities to the end phenotypes described and relevance of pharmacological targets and possible treatments will be considerations throughout.

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.

The Metabolic-Inflammatory Axis in Brain Aging and Neurodegeneration

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452538 Year: Pages: 161 DOI: 10.3389/978-2-88945-253-8 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2018-02-27 16:16:44
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Impairment of energy metabolism is a hallmark of brain aging and several neurodegenerative diseases, such as the Alzheimer’s disease (AD). Age- and disease-related hypometabolism is commonly associated with oxidative stress and they are both regarded as major contributors to the decline in synaptic plasticity and cognition. Neuroinflammatory changes, entailing microglial activation and elevated expression of inflammatory cytokines, also correlate with age-related cognitive decline. It is still under debate whether the mitochondrial dysfunction-induced metabolic deficits or the microglia activation-mediated neuroinflammation is the initiator of the cognitive changes in aging and AD. Nevertheless, multiple lines of evidence support the notion that mitochondrial dysfunction and chronic inflammation exacerbate each other, and these mechanistic diversities have cellular redox dysregulation as a common denominator. This research topic focuses on the role of a metabolic-inflammatory axis encompassing the bioenergetic activity, brain inflammatory responses and their redox regulation in healthy brain aging and neurodegenerative diseases. Dynamic interactions among these systems are reviewed in terms of their causative or in-tandem occurrence and how the systemic environment, –e.g., insulin resistance, diabetes, and systemic inflammation–, impacts on brain function.

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

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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
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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.

Metabolic Control of Brain Homeostasis

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452866 Year: Pages: 204 DOI: 10.3389/978-2-88945-286-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2018-02-27 16:16:44
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Brain function is under metabolic control, which in turn determines the equilibrium of homeostatic systems that affect neuronal and glial networks on the molecular, cellular, and systems levels. The collection of articles ranges from molecules and mechanisms involved in regulating homeostasis and neuronal excitability to therapeutic mechanisms tailored to restore homeostatic function. It also features neurological diseases and novel treatment approaches that are based on metabolic and homeostatic interventions. Together, the collection of articles outlines novel strategies to restore brain function in neurology and highlights limitations of conventional pharmacological approaches. We suggest that restoration of molecular and biochemical networks could lead to a new era of therapeutic opportunities.

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