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The Physiological Functions of the Amyloid Precursor Protein Gene Family

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453559 Year: Pages: 275 DOI: 10.3389/978-2-88945-355-9 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2018-02-27 16:16:45
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The amyloid precursor protein APP plays a key role in the pathogenesis of Alzheimer’s disease (AD), as proteolytical cleavage of APP gives rise to the Aß peptide which is deposited in the brains of Alzheimer patients. Despite this, our knowledge of the normal cell biological and physiological functions of APP and the closely related APLPs is limited. This may have hampered our understanding of AD, since evidence has accumulated that not only the production of the Aß peptide but also the loss of APP-mediated functions may contribute to AD pathogenesis. Thus, it appears timely and highly relevant to elucidate the functions of the APP gene family from the molecular level to their role in the intact organism, i.e. in the context of nervous system development, synapse formation and adult synapse function, as well as neural homeostasis and aging. Why is our understanding of the APP functions so limited? APP and the APLPs are multifunctional proteins that undergo complex proteolytical processing. They give rise to an almost bewildering array of different fragments that may each subserve specific functions. While Aß is aggregation prone and neurotoxic, the large secreted ectodomain APPsa - produced in the non-amyloidogenic a-secretase pathway - has been shown to be neurotrophic, neuroprotective and relevant for synaptic plasticity, learning and memory. Recently, novel APP cleavage pathways and enzymes have been discovered that have gained much attention not only with respect to AD but also regarding their role in normal brain physiology. In addition to the various cleavage products, there is also solid evidence that APP family proteins mediate important functions as transmembrane cell surface molecules, most notably in synaptic adhesion and cell surface signaling. Elucidating in more detail the molecular mechanisms underlying these divers functions thus calls for an interdisciplinary approach ranging from the structural level to the analysis in model organisms. Thus, in this research topic of Frontiers we compile reviews and original studies, covering our current knowledge of the physiological functions of this intriguing and medically important protein family.

Amyloid-beta clearance in Alzheimer's disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194438 Year: Pages: 111 DOI: 10.3389/978-2-88919-443-8 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2016-02-05 17:24:33
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Strong evidence continues to accumulate indicating that amyloid-beta (Aß) is a central part of Alzheimer’s disease (AD) pathogenesis in spite of the negative evidence coming from failed clinical trials. Therefore, mechanisms of clearance of Aß are of great interest in understanding AD pathogenesis and the development of effective treatments. This topic focuses on the issues related to Aß clearance in AD. The topics covered include proteases that degrade Aß and their localization, regulation, and functions. This topic also covers issues related to clearance through uptake by glia and through low-density lipoprotein (LDL) receptor mediated mechanisms. Signal transduction related to AD pathology and clearance is also addressed. Finally, immunotherapy and other novel therapeutic approaches are discussed.

Imaging in Acute Stroke - New Options and State of the Art

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455348 Year: Pages: 65 DOI: 10.3389/978-2-88945-534-8 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Neurology
Added to DOAB on : 2019-01-23 14:53:42
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One in six suffers a stroke during their lifetime and stroke remains the major cause of new onset disability in adulthood. The worldwide burden of stroke is increasing due to an ageing population, however, globally haft of stroke victims are young.Stroke is the clinical diagnosis of an acute vascular incident and covers a multitude of pathophysiological causes. The clinician needs imaging to make decisions on acute treatment as well as to plan a secondary prevention strategy: a non-contrast CT and a Duplex of the carotids followed by an aspirin as a one size fits all strategy does not always provide sufficient support for those decisions.Presently, fast, generally available, and non-invasive imaging provides new possibilities of establishing a cause of stroke, provide specific information on the brain parenchyma – including possibly salvageable tissue and micro-bleeds – as well as allowing for more specific prognostication in acute stroke. This eBook covers both ischemic and haemorrhagic stroke and includes hot topics such as micro-bleeds, salvageable tissue and spot-sign, clinically challenging issues including movement artefacts in MRI as well as an overview of present options including pragmatic and feasible suggestions for an approach to state of the art acute imaging.

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.

Molecular Mechanism of Alzheimer's Disease

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ISBN: 9783039214075 / 9783039214082 Year: Pages: 228 DOI: 10.3390/books978-3-03921-408-2 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-12-09 11:49:16
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Alzheimer’s disease (AD) is an age-related neurological disease that affects tens of millions of people, in addition to their carers. Hallmark features of AD include plaques composed of amyloid beta, as well as neurofibrillary tangles of tau protein. However, despite more than a century of study, the cause of Alzheimer’s disease remains unresolved. The roles of amyloid beta and tau are being questioned and other causes of AD are now under consideration. The contributions of researchers, model organisms, and various hypotheses will be examined in this Special Issue.

Keywords

?-secretase --- amyloid beta --- calcium signaling --- drug target discovery --- endoplasmic reticulum --- inositol 1,4,5-trisphosphate receptor --- ion channel --- oxidative stress --- ryanodine receptor --- therapy --- amyloid-? oligomer --- protein aggregation --- A?O receptors --- Alzheimer’s disease --- neurodegeneration --- amyloid ? --- Alzheimer’s disease --- cognitive function --- dairy products --- dementia --- inflammation --- microglia --- Alzheimer’s disease --- yeast --- Tau --- amyloid ? --- ubiquitin --- aggregation --- oligomerization --- prion --- CDK5R1 --- lncRNAs --- Alzheimer’s disease --- miR-15/107 --- NEAT1 --- HOTAIR --- MALAT1 --- heat shock response --- heat shock protein --- Alzheimer’s disease --- beta amyloid --- yeast --- Alzheimer’s disease --- complement receptor 1 --- CR1 length polymorphism --- CR1 density --- complement C3b/C4b receptor --- complement --- dementia --- molecular biology --- neurosciences --- genetic risk --- Alzheimer’s disease --- brain glucose metabolism --- neuronal differentiation --- neuronal degeneration --- Prolyl isomerases --- Pin1 --- type 2 diabetes --- type 3 diabetes --- miR-34c --- dendritic spine --- Alzheimer’s disease --- Alzheimer’s disease --- positron emission tomography (PET) --- magnetic resonance imaging (MRI) --- Alzheimer’s disease --- cystathionine-?-lyase CTH gene --- DNA methylation --- epigenetics --- epigenome-wide association study --- methylome --- methylenetetrahydrofolate reductase MTHFR gene --- nutrition --- S-adenosylmethionine --- vitamin B complex --- Alzheimer’s disease --- sleep disturbance --- sleep fragmentation --- slow-wave sleep --- amyloid beta --- tau --- proteostasis --- default-mode network --- cognitive behavioral therapy for insomnia --- APOE gene --- apolipoprotein E --- DNA methylation --- mild cognitive impairment --- Hispanics

Marine Glycobiology, Glycomics and Lectins

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ISBN: 9783039218202 / 9783039218219 Year: Pages: 176 DOI: 10.3390/books978-3-03921-821-9 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Biochemistry
Added to DOAB on : 2019-12-09 16:39:37
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Glycans (carbohydrate chains) of marine creatures are rich and diverse in polysaccharides, glycoproteins, and glycolipids. The chains that are metabolized by glycan-related enzymes (glycosyltransferases and glycosidases) are recognized by glycan-binding proteins (lectins) which regulate cellular processes such as growth, differentiation, and death. Marine glycomics that involves the genome and transcriptome accelerates our understanding of the evolution of glycans, glycan-related enzymes, and lectins. From 2017 to 2019, the Special Issue “Marine Glycobiology, Glycomics and Lectins” of the journal Marine Drugs published scientific articles and reviews, on the background of “glycobiology”—that is, glycan-based biosciences. The aim was to promote the discovery of novel biomolecules that contribute to drug development and clinical studies. This has great potential for establishing connections between the fields of both human health and marine life sciences.This book contains 11 scientific papers representing current topics in comprehensive glycosciences related to therapeutic agents from marine natural products, as outlined.

Molecular Modeling in Drug Design

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ISBN: 9783038976141 Year: Pages: 220 DOI: 10.3390/books978-3-03897-615-8 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Chemistry (General) --- Science (General)
Added to DOAB on : 2019-04-05 10:34:31
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Abstract

This book is a printed edition of the Special Issue Molecular Modeling in Drug Design that was published in Molecules

Keywords

hyperlipidemia --- squalene synthase (SQS) --- molecular modeling --- drug discovery --- Traditional Chinese Medicine --- molecular dynamics simulation --- biophenols --- natural compounds --- amyloid fibrils --- Alzheimer’s disease --- ligand–protofiber interactions --- adhesion --- FimH --- rational drug design --- molecular dynamics --- molecular docking --- ligand binding --- EphA2-ephrin A1 --- PPI inhibition --- interaction energy --- in silico screening --- adenosine --- boron cluster --- adenosine receptors --- AR ligands --- aggregation --- promiscuous mechanism --- human ecto-5?-nucleotidase --- virtual screening --- enzymatic assays --- turbidimetry --- dynamic light scattering --- docking --- solvent effect --- binding affinity --- scoring function --- molecular dynamics --- target-focused pharmacophore modeling --- density-based clustering --- structure-based drug design --- AutoGrid --- grid maps --- probe energies --- method development --- steered molecular dynamics --- all-atom molecular dynamics simulation --- resultant dipole moment --- mechanical stability --- protein-peptide interactions --- molecular dynamics --- proteins --- molecular recognition --- protein protein interactions --- artificial intelligence --- deep learning --- neural networks --- property prediction --- quantitative structure-activity relationship (QSAR) --- quantitative structure-property prediction (QSPR) --- de novo design --- adenosine receptor --- metadynamics --- extracellular loops --- allosterism --- molecular dynamics --- cosolvent molecular dynamics --- drug design --- fragment screening --- docking

Curcumin in Health and Disease

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ISBN: 9783039214495 / 9783039214501 Year: Pages: 274 DOI: 10.3390/books978-3-03921-450-1 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Chemistry (General)
Added to DOAB on : 2019-12-09 11:49:15
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The plant-derived polyphenol curcumin has been used in promoting health and combating disease for thousands of years. Its therapeutic effects have been successfully utilized in Ayurvedic and Traditional Chinese Medicine in order to treat inflammatory diseases. Current results from modern biomolecular research reveal the modulatory effects of curcumin on a variety of signal transduction pathways associated with inflammation and cancer. In this context, curcumin’s antioxidant, anti-inflammatory, anti-tumorigenic, and even anti-metastatic activities are discussed. On the cellular level, the reduced activity of several transcription factors (such as NFkB or AP-1) and the suppression of inflammatory cytokines, matrix degrading enzymes, metastasis related genes and even microRNAs are reported. On functional levels, these molecular effects translate into reduced proliferative, invasive, and metastatic capacity, as well as induced tumor cell apoptosis. All these effects have been observed not only in vitro but also in animal models. In combination with anti-neoplastic drugs like Taxol, kinase inhibitors, and radiation therapy, curcumin potentiates the drugs’ therapeutic power and can protect against undesired side effects. Natural plant-derived compounds like curcumin have one significant advantage: They do not usually cause side effects. This feature qualifies curcumin for primary prevention in healthy persons with a predisposition to cancer, arteriosclerosis, or chronic inflammatory diseases. Nonetheless, curcumin is considered safe, although potential toxic effects stemming from high dosages, long-term intake, and pharmacological interactions with other compounds have yet to be assessed. This Special Issue examines in detail and updates current research on the molecular targets, protective effects, and modes of action of natural plant-derived compounds and their roles in the prevention and treatment of human diseases.

Keywords

brain ischemia --- curcumin --- Alzheimer’s disease --- neurodegeneration --- amyloid --- tau protein --- autophagy --- mitophagy --- apoptosis --- genes --- glioblastoma multiforme --- autophagy --- mitophagy --- curcumin --- chaperone-mediated autophagy --- Akt/mTOR signaling --- transmission electron microscopy --- Curcuma longa --- turmeric tuber --- Zingiberaceae --- TLC bioautography --- antimicrobial agents --- ImageJ --- TLC-MS --- hydrostatic counter-current chromatography --- centrifugal partition chromatography --- curcumin --- death receptor --- apoptosis --- curcumin --- anticancer --- structure activity relationship --- cellular pathway --- mechanism of action --- delivery system --- wound --- wound healing --- diet --- nutrition --- micronutrients --- macronutrients --- curcumin --- amino-acids --- vitamins --- minerals --- curcumin --- oxidative metabolites --- inflamm-aging --- cancer --- metabolic reprogramming --- direct protein binding --- IL-17 --- STAT3 --- SHMT2 --- ageing --- anti-cancer --- autophagy --- microbiota --- senescence --- senolytics --- curcumin --- transthyretin --- amyloidosis --- protein aggregation --- protein misfolding --- drug discovery --- curcumin --- renal cell cancer --- tumor growth --- tumor proliferation --- cell cycling --- curcumin --- reflux esophagitis --- gastroprotection --- gastric ulcer --- Helicobacter pylori --- gastric cancer --- curcumin --- complementary medicine --- cancer treatment --- supportive care --- antioxidants --- anti-inflamation --- ulcerative colitis --- Crohn’s disease --- necrotizing enterocolitis --- curcumin --- inflammatory bowel disease --- curcumin --- silica --- chitosan --- nanoparticles --- anti-tumor --- antioxidant activity --- n/a

Diagnosis of Dementia and Cognitive Impairment

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ISBN: 9783039218844 / 9783039218851 Year: Pages: 140 DOI: 10.3390/books978-3-03921-885-1 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General)
Added to DOAB on : 2020-01-07 09:08:26
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In this special issue of Diagnostics, expert contributors have produced up-to-date research studies and reviews on various topics related to the diagnosis of dementia and cognitive impairment. The methods of the assessments discussed extend from simple neurological signs, which may be elicited in the clinical encounter, through cognitive screening instruments, to sophisticated analyses of neuroimaging and cerebrospinal fluid biomarkers of disease. It is hoped that these various methods may facilitate earlier diagnosis of dementia and its subtypes, and provide differential diagnosis of depression and functional cognitive disorders, as a prelude to meaningful interventions.

Special Issue Dedicated to Late Professor Takuo Okuda. Tannins and Related Polyphenols Revisited: Chemistry, Biochemistry and Biological Activities

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ISBN: 9783038978343 / 9783038978350 Year: Pages: 316 DOI: 10.3390/books978-3-03897-835-0 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General)
Added to DOAB on : 2019-06-26 10:09:00
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Antioxidative polyphenols represented by tannins and flavonoids are rich in numerous food sources and traditional natural medicines and currently attracting increased attention in health care and food industries because of their multiple biological activities that are favorable to human health. Commemorating the outstanding achievements on tannins by Dr. Takuo Okuda on the occasion of his passing away in December 2016, his colleagues, friends, and worldwide experts of polyphenol research have contributed 18 papers on their recent study to the Special Issue of Molecules. This book is its reprinted form. This covers reviews of structural features, historical usages, and biological activities of unique class of ellagitannins and condensed tannins, and original articles on the most up-to-date findings on the anticancer effect of green tea catechins, the antivirus effect of tannins comparing with the clinically used drugs, the analytical method of ellagitannins using quantitative NMR, the chemical structures of Hydrangea-blue complex (pigment) and condensed tannins in Ephedra sinica and purple prairie clover, and the relationship of condensed tannins in legumes and grape-marc with methane production in the in vitro ruminant system, and others. This book will be useful to natural product chemists and also to researchers in pharmaceutical and/or food industry.

Keywords

Dittrichia viscosa --- antifungal activities --- Candida spp. --- Malassezia spp. --- Microsporum canis --- Aspergillus fumigates --- Ephedra sinica --- proanthocyanidin --- oligomer --- thiolysis --- phloroglucinolysis --- TDDFT --- ECD --- neuraminidase --- inhibition --- tannins --- oseltamivir carboxylate --- zanamivir --- crystal structure --- molecular interactions --- oenothein B --- ellagitannin --- macrocyclic oligomer --- Onagraceae --- Myrtaceae --- Lythraceae --- antioxidants --- antitumor effect --- immunomodulatory effect --- anti-inflammation --- tannin composition --- purple prairie clover --- conservation method --- protein precipitation --- Escherichia coli --- Cynanchum wilfordii --- phenolic glycoside --- 2-O-?-laminaribiosyl-4-hydroxyacetophenone --- cynandione A --- thin layer chromatography --- Cynanchum auriculatum --- Acacia mearnsii bark --- wattle tannin --- proanthocyanidins --- biological activities --- tannins --- vegetable tanning --- European historic leathers --- colorimetric tests --- spectroscopy --- UV-Vis --- FTIR --- triple-negative breast cancer --- fatty acid synthase --- FASN inhibition --- polyphenolic FASN inhibitors --- (?)-epigallocatechin 3-gallate --- synthetic analogues --- apoptosis --- anticancer activity --- 1H-NMR --- quantitative NMR --- ellagitannin --- Geranium thunbergii --- geraniin --- Aluminum ion --- blue color development --- 5-O-caffeoylquinic acid --- 3-O-glucosyldelphinidin --- Hydrangea macrophylla --- ESI-mass --- metal complex --- Coreopsis lanceolata L. --- chalcone --- flavanone --- flavonol --- aurone --- Horner–Wadsworth–Emmons reaction --- condensed tannin --- bioactivity --- methanogenesis --- grape marc --- fatty acids --- in vitro batch fermentation --- neuroprotection --- PC12 --- NGF --- differentiation --- amyloid-? peptide --- taxanes --- hormesis --- polyphenol --- bamboo leaf extract --- overlay method --- ellagitannin --- structure --- revision --- (?)-epigallocatechin gallate --- immune checkpoint --- interferon-? --- epidermal growth factor --- lung tumor --- proanthocyanidins --- condensed tannins --- thiolysis --- NMR spectroscopy --- ultrahigh-resolution negative mode MALDI-TOF mass spectrometry --- antioxidant --- ORAC assay --- Acacia --- forage legume --- Trapa taiwanensis Nakai --- hydrolysable tannin --- stability --- gallotannin --- ellagitannin

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