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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".

Regulation and targeting of enzymes mediating Parkinson's disease pathogenesis: focus on Parkinson's disease Kinases, GTPases and ATPases

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193998 Year: Pages: 163 DOI: 10.3389/978-2-88919-399-8 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-12-10 11:59:06
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Understanding the molecular pathogenesis of Parkinson’s disease (PD) is a priority in biomedical research and a pre-requisite to improve early disease diagnosis and ultimately to developing disease-modifying strategies. In the past decade and a half, geneticists have identified several genes that are involved in the molecular pathogenesis of PD. They not only identified gene variants segregating with familial forms of PD but also genetic risk factors of sporadic PD via genome-wide association studies (GWAS). Understanding how PD genes and their gene products function holds the promise of unraveling key PD pathogenic processes. Therefore the precise cellular role of PD proteins is currently the subject of intense investigation.Interestingly, a number of PD proteins have enzymatic functions, including kinase, GTPase or ATPase functions. In the context of understanding disease pathogenesis or developing disease-modifying therapies, enzymes possess several useful features. Firstly, enzymes are often key elements of cellular signaling networks, acting as on-off switches to determine signaling intensity. For instance, kinases mediate phosphorylation events, which activate or inactivate their substrates, while GTPases modulate activity of their effector proteins via direct interaction in a GDP/GTP dependent manner. ATPases also control cellular processes through their involvement in cellular energy production and/or in transmembrane transport. Secondly, enzymes are attractive targets for therapeutics development. This is exemplified by the growing number of kinase inhibitors approved for clinical use, while compounds modulating GTPases or ATPases have also been proposed as potential therapeutics. Finally, as elements in cellular signaling networks, enzymes are not generally constitutively active but subject to further regulation through additional signaling components. Knowledge of how PD kinases, GTPases and ATPases are activated or inactivated can aid in understanding how PD signaling networks are deregulated in disease and point to new possibilities in targeting pathological signaling processes. The objective of this research topic is to provide an overview of current knowledge on the regulation of cellular signaling networks of PD kinases, GTPases and ATPases. Both upstream and downstream signaling events will be covered, with a focus on molecular events that can readily be monitored (relevance as disease biomarkers) and have a potential to be modulated (relevance as potential therapeutic target).

CaMKII in Cardiac Health and Disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889192991 Year: Pages: 165 DOI: 10.3389/978-2-88919-299-1 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Medicine (General) --- Therapeutics --- Science (General)
Added to DOAB on : 2015-12-10 11:59:07
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The calcium-calmodulin dependent protein kinases (CaMKs) are a broadly expressed family of calcium-sensitive intracellular kinases, which are responsible for transducing cytosolic calcium signals into phosphorylation-based regulation of proteins and physiological functions. As the multifunctional member of the family, CaMKII has become the most prominent for its roles in the central nervous system and heart, where it controls a diverse range of calcium-dependent processes; from learning and memory at the neuronal synapse, to cellular growth and death in the myocardium. In the heart, CaMKII directly regulates many of the most important ion channels and calcium handling proteins, and controls the expression of an ever-increasing number of transcripts and their downstream products. Functionally, these actions are thought to orchestrate many of the electrophysiologic and contractile adaptations to common cardiac stressors, such as rapid pacing, chronic adrenergic stimulation, and oxidative challenge. In the context of disease, CaMKII has been shown to contribute to a remarkably wide variety of cardiac pathologies, of which heart failure (HF) is the most conspicuous. Hyperactivity of CaMKII is an established contributor to pathological cardiac remodeling, and is widely thought to directly promote arrhythmia and contractile dysfunction during HF. Moreover, several non-failing arrhythmia-susceptible phenotypes, which result from specific genetic channelopathies, functionally mimic constitutive channel phosphorylation by CaMKII. Because CaMKII contributes to both the acute and chronic manifestations of major cardiac diseases, but may be only minimally required for homeostasis in the absence of chronic stress, it has come to be one of the most promising therapeutic drug targets in cardiac biology. Thus, development of more specific and deliverable small molecule antagonists remains a key priority for the field. Here we provide a selection of articles to summarize the state of our knowledge regarding CaMKII in cardiac health and disease, with a particular view to highlighting recent developments in CaMKII activation, and new targets in CaMKII-mediated control of myocyte physiology.

Protein Phosphorylation in Health and Disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199006 Year: Pages: 122 DOI: 10.3389/978-2-88919-900-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Genetics
Added to DOAB on : 2016-01-19 14:05:46
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Protein phosphorylation is one of the most abundant reversible post-translational modifications in eukaryotes. It is involved in virtually all cellular processes by regulating protein function, localization and stability and by mediating protein-protein interactions. Furthermore, aberrant protein phosphorylation is implicated in the onset and progression of human diseases such as cancer and neurodegenerative disorders. In the last years, tens of thousands of in vivo phosphorylation events have been identified by large-scale quantitative phospho-proteomics experiment suggesting that a large fraction of the proteome might be regulated by phosphorylation. This data explosion is increasingly enabling the development of computational approaches, often combined with experimental validation, aiming at prioritizing phosphosites and assessing their functional relevance. Some computational approaches also address the inference of specificity determinants of protein kinases/phosphatases and the identification of phosphoresidue recognition domains. In this context, several challenging issues are still open regarding phosphorylation, including a better understanding of the interplay between phosphorylation and allosteric regulation, agents and mechanisms disrupting or promoting abnormal phosphorylation in diseases, the identification and modulation of novel phosphorylation inhibitors, and so forth. Furthermore, the determinants of kinase and phosphatase recognition and binding specificity are still unknown in several cases, as well as the impact of disease mutations on phosphorylation-mediated signaling. The articles included in this Research Topic illustrate the very diverse aspects of phosphorylation, ranging from structural changes induced by phosphorylation to the peculiarities of phosphosite evolution. Some also provide a glimpse into the huge complexity of phosphorylation networks and pathways in health and disease, and underscore that a deeper knowledge of such processes is essential to identify disease biomarkers, on one hand, and design more effective therapeutic strategies, on the other.

Regulatory potential of post-translational modifications in bacteria

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196104 Year: Pages: 204 DOI: 10.3389/978-2-88919-610-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Microbiology
Added to DOAB on : 2016-08-16 10:34:25
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Post-translational modifications (PTMs) are widely employed by all living organisms to control the enzymatic activity, localization or stability of proteins on a much shorter time scale than the transcriptional control. In eukarya, global analyses consistently reveal that proteins are very extensively phosphorylated, acetylated and ubiquitylated. Glycosylation and methylation are also very common, and myriad other PTMs, most with a proven regulatory potential, are being discovered continuously. The emergent picture is that PTM sites on a single protein are not independent; modification of one residue often affects (positively or negatively) modification of other sites on the same protein. The best example of this complex behavior is the histone “bar-code” with very extensive cross-talk between phosphorylation, acetylation and methylation sites.Traditionally it was believed that large networks of PTMs exist only in complex eukaryal cells, which exploit them for coordination and fine-tuning of various cellular functions. PTMs have also been detected in bacteria, but the early examples focused on a few important regulatory events, based mainly on protein phosphorylation. The global importance (and abundance) of PTMs in bacterial physiology was systematically underestimated. In recent years, global studies have reported large datasets of phosphorylated, acetylated and glycosylated proteins in bacteria. Other modifications of bacterial proteins have been recently described: pupylation, methylation, sirtuin acetylation, lipidation, carboxylation and bacillithiolation. As the landscape of PTMs in bacterial cells is rapidly expanding, primarily due to advances of detection methods in mass spectrometry, our research field is adapting to comprehend the potential impact of these modifications on the cellular physiology. The field of protein phosphorylation, especially of the Ser/Thr/Tyr type, has been profoundly transformed. We have become aware that bacterial kinases phosphorylate many protein substrates and thus constitute regulatory nodes with potential for signal integration. They also engage in cross-talk and eukaryal-like mutual activation cascades. The regulatory potential of protein acetylation and glycosylation in bacteria is also rapidly emerging, and the cross-talk between acetylation and phosphorylation has been documented. This topic deals with the complexity of the PTM landscape in bacteria, and focus in particular on the physiological roles that PTMs play and methods to study them. The topic is associated to the 1st International Conference on Post-Translational Modifications in Bacteria (September 9-10, 2014, Göttingen, Germany).

Signal Transduction in Stomatal Guard Cells

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451678 Year: Pages: 105 DOI: 10.3389/978-2-88945-167-8 Language: English
Publisher: Frontiers Media SA
Subject: Botany --- Science (General)
Added to DOAB on : 2017-08-28 14:01:09
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Stomata, the tiny pores on leaf surface, are the gateways for CO2 uptake during photosynthesis as well as water loss in transpiration. Further, plants use stomatal closure as a defensive response, often triggered by elicitors, to prevent the entry of pathogens. The guard cells are popular model systems to study the signalling mechanism in plant cells. The messengers that mediate closure upon perception of elicitors or microbe associated molecular patterns (MAMPs) are quite similar to those during ABA effects. These components include reactive oxygen species (ROS), nitric oxide (NO), cytosolic pH and intracellular Ca2+. The main components are ROS, NO and cytosolic free Ca2+. The list extends to others, such as G-proteins, protein phosphatases, protein kinases, phospholipids and ion channels. The sequence of these signalling components and their interaction during stomatal signalling are complex and quite interesting. The present e-Book provides a set of authoritative articles from ‘Special Research Topic’ on selected areas of stomatal guard cells. In the first set of two articles, an overview of ABA and MAMPs as signals is presented. The next set of 4 articles, emphasize the role of ROS, NO, Ca2+ as well as pH, as secondary messengers. The next group of 3 articles highlight the recent advances on post-translational modification of guard cell proteins, with emphasis on 14-3-3 proteins and MAPK cascades. The last article described the method to isolate epidermis of grass species and monitor stomatal responses to different signals. Our e-Book is a valuable and excellent source of information for all those interested in guard cell function as well as signal transduction in plant cells.

Neuroproteomics

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ISBN: 9783039281060 9783039281077 Year: Pages: 318 DOI: 10.3390/books978-3-03928-107-7 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General) --- Neurology
Added to DOAB on : 2020-04-07 23:07:08
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The Neuroproteomics Special Issue overviews the unique challenges that must be addressed to carry out meaningful MS/proteomics analyses on neural tissues and the technologies that are available to meet these challenges. The articles on Alzheimer’s disease, addiction, and schizophrenia illustrate how MS/proteomics technologies can be used to improve our ability to diagnose and understand the molecular basis for neurological diseases. Several articles will be of interest to investigators beyond the field of neurological disorders. The review on the discovery of biofluid biomarkers of neurodegenerative dementias will be of interest to investigators searching for other disease biomarkers. Similarly, the review on the role of neuroproteomics in elucidating mechanisms of drug addiction provides an overview of the utility of MS/proteomics approaches for addressing critical questions in addiction neuroscience that should be applicable to investigators involved in virtually any area of biomedical research. Likewise, the article on developing targeted MS approaches for quantifying postsynaptic density proteins will be useful for any investigator who wishes to design targeted assays for virtually any protein. Finally, the peroxidase-mediated proximity labeling technology, described in the article on mapping the proteome of the synaptic cleft, will be of interest to investigators interested in mapping other spatially restricted proteomes.

Keywords

proteomics --- basal ganglia --- synapses --- synapse specificity --- neuronal circuits --- axons --- dendrites --- neurodegeneration --- synapse --- postsynaptic --- proteome --- mass spectrometry --- protein interaction networks --- connectome --- neurodegeneration --- Alzheimer’s disease --- cerebrospinal fluid --- plasma --- serum --- proteomics --- biomarkers --- LC-MS/MS --- cocaine --- addiction --- cytokine --- neuroimmune --- ventral tegmental area --- peptidylglycine ?-amidating monooxygenase --- cilia --- mating --- signal peptide --- prohormone convertase --- carboxypeptidase --- matrix metalloproteinase --- subtilisin --- pherophorin --- morphine --- opioid receptors --- conformational antibody --- analgesia --- GPCR signaling --- phosphorylation --- AMPA receptor complex --- transmembrane AMPA receptor regulatory protein --- synaptic plasticity --- adolescence --- corticosterone --- proteomics --- yohimbine --- progressive ratio --- reinstatement --- ethanol --- nicotinic receptor --- CaMKII --- PKA --- quantitative phosphoproteomics --- mouse --- phosphorylation --- nicotine --- proteomics --- proteome --- mass spectrometry --- Alzheimer’s disease --- protein aggregation --- laser capture microdissection --- splicing --- U1 snRNP --- synapse --- synaptic cleft --- trans-synaptic adhesion --- proximity labeling --- SynCAM --- Cadm --- Receptor-type tyrosine-protein phosphatase zeta --- R-PTP-zeta --- Ptprz1 --- neuroproteome --- drug abuse --- neuropeptidomics --- phosphorylation --- interactome --- cell type --- neuroscience --- proteomics --- mass spectrometry --- neuron --- proximity labeling --- affinity chromatography --- neuroproteomics --- biotinylation --- amphetamine --- spinophilin --- protein phosphatase-1 --- dopamine --- striatum --- mass spectroscopy --- bioinformatics --- FGF14 --- voltage gated channels --- schizophrenia --- autism --- Alzheimer’s Disease --- sex-specific differences --- synaptic plasticity --- cognitive impairment --- excitatory/inhibitory tone --- n/a --- postsynaptic density --- PSD --- parallel reaction monitoring --- PRM --- targeted proteomics --- data-independent acquisition --- DIA --- quantitative mass spectrometry --- n/a

Advanced Flame Retardant Materials

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ISBN: 9783039283507 9783039283514 Year: Pages: 190 DOI: 10.3390/books978-3-03928-351-4 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Physics (General) --- Science (General)
Added to DOAB on : 2020-04-07 23:07:09
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Recent disasters caused by the spread of fire in buildings and in transportations remind us of the importance of fire protection. Using flame-retardant materials is one important element of the firefighting strategy, which aims to prevent fire development and propagation. These materials are used in different applications, such as in textiles, coatings, foams, furniture, and cables. The development of more efficient and environmentally friendly flame-retardant additives is an active multidisciplinary approach that has attracted a great deal of interest. Studies have aimed at the development of new, sustainable, and flame-retardant additives/materials, providing high performance and low toxicity. Also studied were their properties during ageing and recycling, as well as modeling physical and chemical processes occuring before ignition and during their combustion. The development of sustainable flame retardants and understanding their modes of action provide a strong link between these topics and cover many fields from organic chemistry, materials engineering, and toxicology, to physics and mathematics.

In-Cell NMR Spectroscopy: Biomolecular Structure and Function

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ISBN: 9783039282548 / 9783039282555 Year: Pages: 152 DOI: 10.3390/books978-3-03928-255-5 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2020-06-09 16:38:57
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This Special Issue examines state-of-the-art in-cell NMR spectroscopy as it relates to biological systems of increasing complexity. The compendia of research and recent innovations from prominent laboratories in the field of solid state and solution in-cell NMR spectroscopy, metabolomics and technology development are presented. The work establishes in-cell NMR spectroscopy as the premier method for determining the structures and interaction capabilities of biological molecules at high resolution within the delicately intricate interior of living cells, and the means of utilizing cells as living laboratories to directly assess the effects of exogenous and endogenous stimuli on cell physiology.]

Benefits of Resveratrol Supplementation

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ISBN: 9783039212750 9783039212767 Year: Pages: 260 DOI: 10.3390/books978-3-03921-276-7 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Nutrition and Food Sciences
Added to DOAB on : 2019-08-28 11:21:27
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In recent years, great attention has been paid to polyphenols due to their positive effects on health. One of the most widely-studied phenolic compounds is resveratrol. This molecule, which is naturally present in some foods, shows beneficial effects on various physiological and biochemical processes, thus representing a potential tool for the prevention or the treatment of diseases highly prevalent in our society. Several of these beneficial effects have been observed in human beings, but others only in pre-clinical studies so far, and therefore, it is mandatory to continue with the scientific research in this field. Indeed, new knowledge concerning these issues could enable the development of novel functional foods or nutraceuticals, incorporating resveratrol, suitable for preventing or treating diseases such as cancer, cardiovascular diseases, obesity, dislipemia, insulin resistance and diabetes, liver diseases, etc.

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