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Tau oligomers

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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
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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".

Metals and neurodegeneration: Restoring the balance

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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
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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.

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.

New Perspectives in Neurosteroids action: a Special Player Allopregnanolone

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195558 Year: Pages: 86 DOI: 10.3389/978-2-88919-555-8 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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Early in the 80’s date the first observations on the existence of hormonal steroids that may be synthesized and act in the nervous system. In order to refer to these endogenous steroids, proved important to control both central and peripheral nervous system, it was proposed the term “neurosteroids” (NSs). Over the years, their importance in regulating the physiological functions of neuronal and glial cells increased progressively. These steroids can be involved in several pathophysiological conditions such as depression, anxiety, premenstrual syndrome (PMS), schizophrenia and Alzheimer disease. Among the different classes of NSs, the progestagens revealed particularly important. The progesterone metabolite 5a-pregnan-3a-ol-20-one, also named tetrahydroprogesterone or allopregnanolone (ALLO) was one of the first most important steroid that was originally shown to act as neurosteroid. ALLO is synthesized through the action of the 5aR-3a-HSD, which converts P into DHP and subsequently, via a bidirectional reaction, into ALLO. NSs exert complex effects in the nervous system through ‘classic’, genomic, and ‘non-classic’, non-genomic actions. ALLO displays a rapid ‘non-genomic’ effect, which mainly involves the potent modulation of the GABA type A (GABA-A) receptor function. Recently a membrane receptor has been identified as target for ALLO effects, i.e. the membrane progesterone receptors (mPRs) that are able to activate a signalling cascade through G protein dependent mechanisms. By these ways, ALLO is able to modulate several cell functions, acting as neurogenic molecule on neural progenitor cells, as well as by activating proliferation and differentiation of glial cells in the central and peripheral nervous system. In this topic, we review the most recent acquisitions in the field of neurosteroids, focusing our attention on ALLO because its effects on the physiology of neurons and glial cells of the central and peripheral nervous system are intriguing and could potentially lead to the development of new strategies for neuroprotection and/or regeneration of injured nervous tissues and for the treatment of neuropsychiatric disorders.

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.

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.

Innovative Extraction Techniques and Hyphenated Instrument Configuration for Complex Matrices Analysis

Authors: --- ---
ISBN: 9783039210848 / 9783039210855 Year: Pages: 308 DOI: 10.3390/books978-3-03921-085-5 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Technology (General) --- Chemical Engineering
Added to DOAB on : 2019-06-26 08:44:06
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The present Special Issue, “Innovative Extraction Techniques and Hyphenated Instrument Configuration for Complex Matrices Analysis”, aims to collect and to disseminate some of the most significant and recent contributions in the interdisciplinary area of innovative extraction procedures from complex matrices followed by validated analytical methods using hyphenated instrument configurations to support the optimization of the whole process and the scale-up possibility

Keywords

branched-chain keto acids --- serum --- muscle --- HPLC-Q-TOF/MS --- wood --- odor --- volatile organic compounds --- gas chromatography-olfactometry --- Wuyi Rock tea --- quality --- UPLC-QTOF MS --- UPLC-QqQ MS --- metabolite profiling --- metabolomics --- cluster analysis --- cultivars --- Lycium ruthenicun --- flavonoid --- ruthenicunoid A --- SIRT1 --- Asphodeline lutea --- HPLC-PDA --- heavy metals --- tyrosinase --- diabetes --- neurodegenerative disease --- color analysis --- pigments --- MAE --- HPLC-PDA --- SFE --- Thymus algeriensis --- rare earth elements --- flow injection --- inductively coupled plasma-mass spectrometry --- seawater --- Hericium erinaceuns mycelium --- high-speed counter-current chromatography (HSCCC) --- genistein --- daidzein --- Fe3O4 --- modification --- alginate --- alkaloid --- ultrasound assisted extraction --- gelatin --- actinidin --- bovine hide --- physicochemical properties --- gel strength --- Semen Cuscutae --- ultra-high-performance liquid chromatography coupled to electrospray ionization mass spectrometry --- chlorogenic acids --- flavonoids --- steamed Panax notoginseng --- saponins --- extraction --- optimization --- antioxidant activity --- response surface methodology --- hematopoiesis --- microwave processing --- response surface methodology --- minor ginsenosides --- blood-enriching activity --- hemostatic activity --- ionic liquids --- sample preparation --- microextraction --- solid-phase microextraction --- dispersive liquid-liquid microextraction --- single-drop microextraction --- stir bar sorptive extraction --- stir cake sorptive extraction --- rosuvastatin --- metformin --- HILIC --- LC-MS --- therapeutic drug monitoring --- oolong tea --- Tieguanyin tea cultivar --- metabolite profiling --- UPLC-QTOF MS --- metabolomics --- Ajuga genevensis --- near-infrared spectroscopy --- dry extract --- fluid bed process --- microNIR --- in-line monitoring --- total polyphenolic content --- antioxidant --- flavonoids --- mouse melanoma B16 cells --- Panax notoginseng --- surfactant --- n/a --- ultra-high-performance liquid chromatography tandem mass spectrometry --- GHB --- GHB glucuronide --- nails --- endogenous values --- walnut septum --- polyphenols --- phytosterols --- HPLC-MS/MS --- Ultra-Turrax extraction --- biological activity --- antioxidant activity --- experimental design --- optimization --- phytochemicals

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