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Towards Mechanism-based Treatments for Fragile X Syndrome

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ISBN: 9783039215058 / 9783039215065 Year: Pages: 250 DOI: 10.3390/books978-3-03921-506-5 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-12-09 11:49:15
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Abstract

It has been more than 25 years since the identification of the FMR1 gene and the demonstration of the causative role of CGG-repeat expansion in the disease pathology of fragile X syndrome (FXS), but the underlying mechanisms involved in the expansion mutation and the resulting gene silencing still remain elusive. Our understanding of the pathways impacted by the loss of FMRP function has grown tremendously, and has opened new avenues for targeted treatments for FXS. However, the failure of recent clinical trials that were based on successful preclinical studies using the Fmr1 knockout mouse model has forced the scientific community to revisit clinical trial design and identify objective outcome measures. There has also been a renewed interest in restoring FMR1 gene expression as a possible treatment approach for FXS. This special issue of Brain Sciences highlights the progress that has been made towards understanding the disease mechanisms and how this has informed the development of treatment strategies that are being explored for FXS.

Keywords

fragile X syndrome --- clinical trials --- targeted treatments --- drug development --- fragile X syndrome --- clinical trials --- treatment development --- best practices --- fragile X syndrome --- newborn screening --- early identification --- fragile X syndrome --- X chromosome --- females --- FMR1 --- anxiety --- avoidance --- cognition --- behavior --- brain --- Fragile X --- FMRP --- Fxr2 --- Fmr1 --- fragile X syndrome --- executive function --- working memory --- set-shifting --- cognitive flexibility --- inhibitory control --- attention --- planning --- processing speed --- Fragile X syndrome 1 --- Fragile X-associated Tremor/Ataxia Syndrome 2 --- CRISPR 3 --- Trinucleotide Repeat 4 --- Gene editing --- fragile X syndrome --- FMR1 gene --- voice of the person --- voice of the patient --- characteristics that have the greatest impact --- developmental disorders --- fragile X syndrome --- language development --- automated vocal analysis --- adeno-associated virus --- autism spectrum disorders --- cerebral spinal fluid --- fragile X mental retardation protein --- neurodevelopmental disorders --- viral vector --- fragile X syndrome --- gene reactivation --- RNA:DNA hybrid --- FMRP --- histone methylation --- DNA methylation --- FMR1 --- PRC2 --- fragile X syndrome --- unstable repeat diseases --- epigenetic gene silencing --- DNA methylation --- repeat instability --- pluripotent stem cells --- CGG Repeat Expansion Disease --- DNA instability --- expansion --- contraction --- mismatch repair (MMR) --- base excision repair (BER) --- transcription coupled repair (TCR) --- double-strand break repair (DSBR) --- Non-homologous end-joining (NHEJ) --- mosaicism --- protein synthesis --- Fragile X Syndrome --- biomarker --- iPSC --- fibroblast --- lymphoblast --- fragile X syndrome --- molecular biomarkers --- FMR1 --- FMRP --- intellectual disability --- Fmr1 KO mouse --- ASD --- n/a

Polyamine Metabolism in Disease and Polyamine-Targeted Therapies

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ISBN: 9783039211524 / 9783039211531 Year: Pages: 240 DOI: 10.3390/books978-3-03921-153-1 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-12-09 11:49:15
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Polyamines are ubiquitous polycations essential for all cellular life. The most common polyamines in eukaryotes, spermine, spermidine, and putrescine, exist in millimolar intracellular concentrations that are tightly regulated through biosynthesis, catabolism, and transport. Polyamines interact with, and regulate, negatively charged macromolecules, including nucleic acids, proteins, and ion channels. Accordingly, alterations in polyamine metabolism affect cellular proliferation and survival through changes in gene expression and transcription, translation, autophagy, oxidative stress, and apoptosis. Dysregulation of these multifaceted polyamine functions contribute to multiple disease processes, thus their metabolism and function have been targeted for preventive or therapeutic intervention. The correlation between elevated polyamine levels and cancer is well established, and ornithine decarboxylase, the rate-limiting biosynthetic enzyme in the production of putrescine, is a bona fide transcriptional target of the Myc oncogene. Furthermore, induced polyamine catabolism contributes to carcinogenesis that is associated with certain forms of chronic infection and/or inflammation through the production of reactive oxygen species. These and other characteristics specific to cancer cells have led to the development of polyamine-based agents and inhibitors aimed at exploiting the polyamine metabolic pathway for chemotherapeutic and chemopreventive benefit. In addition to cancer, polyamines are involved in the pathologies of neurodegenerative diseases including Alzheimer’s and Parkinson’s, parasitic and infectious diseases, wound healing, ischemia/reperfusion injuries, and certain age-related conditions, as polyamines are known to decrease with age. As in cancer, polyamine-based therapies for these conditions are an area of active investigation. With recent advances in immunotherapy, interest has increased regarding polyamine-associated modulation of immune responses, as well as potential immunoregulation of polyamine metabolism, the results of which could have relevance to multiple disease processes. The goal of this Special Issue of Medical Sciences is to present the most recent advances in polyamine research as it relates to health, disease, and/or therapy.

Keywords

polyamine transport inhibitor --- Drosophila imaginal discs --- difluoromethylorthinine --- DFMO --- polyamine --- cancer --- metabolism --- difluoromethylornithine --- polyamine transport inhibitor --- pancreatic ductal adenocarcinoma --- curcumin --- diferuloylmethane --- ornithine decarboxylase --- polyamine --- NF-?B --- chemoprevention --- carcinogenesis --- polyphenol --- ornithine decarboxylase --- polyamines --- untranslated region --- polyamines --- ?-difluoromethylornithine --- polyamine transport system --- melanoma --- mutant BRAF --- spermine --- spermidine --- putrescine --- polyamine metabolism --- mast cells --- eosinophils --- neutrophils --- M2 macrophages --- airway smooth muscle cells --- Streptococcus pneumoniae --- polyamines --- pneumococcal pneumonia --- proteomics --- capsule --- complementation --- metabolism --- cadaverine --- polyamines --- ornithine decarboxylase --- difluoromethylornithine --- eflornithine --- DFMO --- African sleeping sickness --- hirsutism --- colorectal cancer --- neuroblastoma --- aging --- atrophy --- autophagy --- oxidative stress --- polyamines --- skeletal muscle --- spermidine --- spermine oxidase --- transgenic mouse --- immunity --- T-lymphocytes --- B-lymphocytes --- tumor immunity --- metabolism --- epigenetics --- autoimmunity --- polyamines --- ornithine decarboxylase --- polyamine analogs --- spermidine/spermine N1-acetyl transferase --- spermine oxidase --- bis(ethyl)polyamine analogs --- breast cancer --- MCF-7 cells --- transgenic mice --- polyamines --- MYC --- protein synthesis in cancer --- neuroblastoma --- protein expression --- antizyme 1 --- ornithine decarboxylase --- CRISPR --- human embryonic kidney 293 (HEK293) --- cell differentiation --- DFMO --- ornithine decarboxylase --- osteosarcoma --- polyamines --- polyamines --- polyamine metabolism --- antizyme --- antizyme inhibitors --- ornithine decarboxylase --- Snyder-Robinson Syndrome --- spermine synthase --- X-linked intellectual disability --- polyamine transport --- spermidine --- spermine --- transglutaminase

AMP-Activated Protein Kinase Signalling

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ISBN: 9783038976622 Year: Pages: 452 DOI: 10.3390/books978-3-03897-663-9 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-03-21 14:08:22
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Abstract

Starting from a kinase of interest, AMP-activated protein kinase (AMPK) has gone far beyond an average biomolecule. Being expressed in all mammalian cell types and probably having a counterpart in every eukaryotic cell, AMPK has attracted interest in virtually all areas of biological research. Structural and biophysical insights have greatly contributed to a molecular understanding of this kinase. From good old protein biochemistry to modern approaches, such as systems biology and advanced microscopy, all disciplines have provided important information. Thus, multiple links to cellular events and subcellular localizations have been established. Moreover, the crucial involvement of AMPK in human health and disease has been evidenced. AMPK accordingly has moved from an interesting enzyme to a pharmacological target. However, despite our extensive current knowledge about AMPK, the growing community is busier than ever. This book provides a snapshot of recent and current AMPK research with an emphasis on work providing molecular insight, including but not limited to novel physiological and pathological functions, or regulatory mechanisms. Up-to-date reviews and research articles are included.

Keywords

exercise --- glucose uptake --- AMP-activated protein kinase --- TBC1D4 --- AS160 --- AMP-activated protein kinase --- developmental origins of health and disease (DOHaD) --- hypertension --- kidney disease --- nutrient-sensing signals --- oxidative stress --- renin-angiotensin system --- AMPK --- autophagy --- co-expression --- microarrays --- 3T3-L1 --- adipocyte --- differentiation --- AMPK --- tight junctions --- epithelial cells --- ZO-1 --- par complex --- MDCK --- nectin-afadin --- adherent junctions --- TAK1 --- AMPK --- phosphorylation --- AMPK kinase --- endothelial nitric-oxide synthase --- vasodilation --- phenylephrine --- vasoconstriction --- endothelial cells --- ionomycin --- AMPK --- liver --- lipid metabolism --- fatty acid oxidation --- indirect calorimetry --- atrophy --- regrowth --- sirtuin 1 (SIRT1) --- peroxisome proliferator-activated receptor gamma coactivator 1-? (PGC1?) --- heat shock protein --- fiber-type --- AMPK --- monocytes --- macrophages --- differentiation --- autophagy --- AML --- MDS --- CML --- CMML --- pregnancy --- catechol-O-methyltransferase --- 2-methoxyestradiol --- preeclampsia --- gestational diabetes mellitus --- AMPK --- IL-1? --- NLRP3 --- nutrition --- dietary fatty acids --- metabolic-inflammation --- nutrigenomics --- AMPK --- LKB1 --- autophagy --- proteasome --- hypertrophy --- atrophy --- skeletal muscle --- AICAR --- mTOR --- protein synthesis --- AMPK --- epigenetics --- chromatin remodeling --- histone modification --- DNA methylation --- medulloblastoma --- sonic hedgehog --- AMPK --- AMP-activated protein kinase (AMPK) --- spermatozoa --- motility --- mitochondria --- membranes --- signaling --- stress --- assisted reproduction techniques --- AMP-activated protein kinase --- epigenetics --- protein acetylation --- KATs --- HDACs --- acetyl-CoA --- NAD+ --- AMP-activated protein kinase --- glycogen --- exercise --- metabolism --- cellular energy sensing --- energy utilization --- liver --- skeletal muscle --- metabolic disease --- glycogen storage disease --- resveratrol --- AMPK --- hepatocyte --- liver --- steatosis --- transporter --- carrier --- pump --- membrane --- energy deficiency --- AMPK --- infection --- mycobacteria --- host defense --- energy metabolism --- AMPK --- activation loop --- AID --- ?-linker --- ?-linker --- CBS --- LKB1 --- CaMKK2 --- ?RIM --- hypothalamus --- adenosine monophosphate-activated protein kinase --- adipose tissue --- food intake --- adaptive thermogenesis --- beiging --- AMPK --- HDAC4/5 --- p70S6K --- MyHC I(?), motor endplate remodeling --- soleus muscle --- mechanical unloading --- hindlimb suspension --- AMPK --- synaptic activation --- PKA --- CREB --- soluble Adenylyl cyclase --- Immediate early genes --- transcription --- AMPK --- autophagy --- metabolism --- mTOR --- ULK --- AMP-activated protein kinase --- protein kinase B --- Akt --- insulin signalling --- A769662 --- endothelial function --- n/a

Marine Bioactive Peptides: Structure, Function, and Therapeutic Potential

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ISBN: 9783039215324 / 9783039215331 Year: Pages: 442 DOI: 10.3390/books978-3-03921-533-1 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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This Special Issue Book, “Marine Bioactive Peptides: Structure, Function, andTherapeutic Potential"" includes up-to-date information regarding bioactivepeptides isolated from marine organisms. Marine peptides have been found invarious phyla, and their numbers have grown in recent years. These peptidesare diverse in structure and possess broad-spectrum activities that have greatpotential for medical applications. Various marine peptides are evolutionaryancient molecular factors of innate immunity that play a key role in host defense.A plethora of biological activities, including antibacterial, antifungal, antiviral,anticancer, anticoagulant, endotoxin-binding, immune-modulating, etc., makemarine peptides an attractive molecular basis for drug design. This Special IssueBook presents new results in the isolation, structural elucidation, functionalcharacterization, and therapeutic potential evaluation of peptides found inmarine organisms. Chemical synthesis and biotechnological production of marinepeptides and their mimetics is also a focus of this Special Issue Book.

Keywords

sea cucumber --- ACE-inhibitory peptide --- molecular docking --- structure-activity relationship --- plastein reaction --- Gracilariopsis lemaneiformis --- ACE-inhibitory activity --- peptide --- molecular docking --- SHRs --- prostate cancer --- Anthopleura anjunae oligopeptide --- DU-145 cells --- PI3K/AKT/mTOR signaling pathway --- cod skin --- NA-inhibitory peptide --- influenza virus --- neuraminidase --- molecular docking --- adsorption --- host defense peptide --- antimicrobial peptide --- anti-LPS factor --- host?microbe relationship --- functional diversity --- invertebrate immunity --- crustacean --- antimicrobial activity --- antimicrobial peptide --- polychaeta --- innate immunity --- BRICHOS domain --- recombinant peptide --- ?-helix --- Rana-box --- nuclear magnetic resonance (NMR) --- antimicrobial peptide --- cytotoxicity --- ?-hairpin --- polyphemusins --- tachyplesins --- cell death --- signaling pathways --- Neptunea arthritica cumingii --- multi-functional peptides --- antioxidant activity --- ACE-inhibitory activity --- anti-diabetic activity --- Arenicola marina --- antimicrobial peptides --- arenicin --- complement --- C3a --- acid-sensing ion channel --- animal models --- pain relief --- toxin --- Ugr 9-1 --- APETx2 --- hairtail (Trichiurus japonicas) --- muscle --- peptide --- antioxidant activity --- half-fin anchovy hydrolysates --- Maillard reaction products --- antibacterial peptide --- identification --- self-production of hydrogen peroxide --- membrane damage --- Perinereis aibuhitensis --- decapeptide --- lung cancer --- cell proliferation --- apoptosis --- conotoxins --- conopeptides --- computational studies --- molecular dynamics --- machine learning --- docking --- review --- drug design --- ion channels --- Conus --- conotoxin --- transcriptome sequencing --- phylogeny --- venom duct --- abalone --- peptide --- vasculogenic mimicry --- metastasis --- MMPs --- HIF-1? --- dexamethasone --- myotube atrophy --- protein synthesis --- proteolytic system --- Pyropia yezoensis peptide --- PYP15 --- QAGLSPVR --- antihypertensive effect --- Caco-2 cell monolayer --- transport routes --- oyster zinc-binding peptide --- peptide-zinc complex --- caco-2 cells --- intestinal absorption --- zinc bioavailability --- Chlorella pyrenoidosa protein hydrolysate (CPPH) --- Chlorella pyrenoidosa protein hydrolysate-calcium chelate (CPPH-Ca) --- calcium absorption --- gene expression --- gut microbiota --- cone snails --- conotoxins --- ion channels --- function --- structure --- marine peptides --- arenicin-1 --- molecular symmetry --- structure–activity relationship --- antibacterial --- cytotoxic --- chemical synthesis --- molecular dynamics --- tilapia --- HUVEC --- angiotensin II --- NF-?B --- Nrf2 --- endothelial dysfunction --- conotoxin --- cone snail --- Conus --- Conus ateralbus --- Kalloconus --- n/a

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2019 (4)