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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 precursor protein --- Amyloid precursor-like protein --- Alzheimers disease --- animal model --- synaptogenesis --- synaptic adhesion --- synaptic plasticity --- spines --- learning and memory --- neuroprotection

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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.

acute stroke --- ischemic stroke --- hemorrhagic stroke --- intracerebral hemorrage --- cerebral amyloid angiopathy --- spot-sign

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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.

?-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

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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.

HddSBL --- oncolytic vaccinia virus --- glioblastoma --- adverse effects --- TTL --- oncolytic vaccinia virus --- viral replication --- ERK --- ?-galactosidase --- recombinant --- thermostable --- transglycosylation --- galactooligosaccharides --- Marinomonas --- Pattalus mollis --- fucosylated glycosaminoglycan --- fucan sulfate --- physicochemical characteristics --- anticoagulant activities --- Alzheimer’s disease --- amyloid-? --- BACE1 --- ?-secretase --- glycosaminoglycan --- heparan sulphate --- heparin --- Portunus pelagicus --- nematocyst discharge process --- theoretical model --- polysialic acid (polySia) --- nematogalectin --- nanomedical devices --- fucoidan --- therapeutic effects --- bioactivity --- anti-viral --- apoptosis-related genes --- Ehrlich ascites carcinoma --- toxicity --- lectin --- MytiLec-1 --- Mytilus galloprovincialis --- malignant glioma --- oligo-fucoidan --- differentiation induction --- epigenetic modification --- DNA methyltransferases --- Fucus distichus subsp. evanescens --- fucoidan --- retinal pigment epithelium --- VEGF --- oxidative stress --- phagocytosis --- innate immunity --- lectins --- complement system --- C1q --- bivalve mollusks --- tandem duplication --- pattern recognition receptors

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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.

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