Search results for "Cholesterol"

showing 10 items of 1211 documents

Statins and the squalene synthase inhibitor zaragozic acid stimulate the non-amyloidogenic pathway of amyloid-beta protein precursor processing by su…

2010

Cholesterol-lowering drugs such as statins influence the proteolytic processing of the amyloid-beta protein precursor (AbetaPP) and are reported to stimulate the activity of alpha-secretase, the major preventive secretase of Alzheimer's disease. Statins can increase the alpha-secretase activity by their cholesterol-lowering properties as well as by impairment of isoprenoids synthesis. In the present study, we elucidate the contribution of these pathways in alpha-secretase activation. We demonstrate that zaragozic acid, a potent inhibitor of squalene synthase which blocks cholesterol synthesis but allows synthesis of isoprenoids, also stimulates alpha-secretase activity. Treatment of human n…

ADAM10Blotting Westernchemistry.chemical_compoundSqualeneADAM10 ProteinAmyloid beta-Protein PrecursorCell Line TumormedicineHumansLovastatinRNA Small InterferingProtein precursorLuciferasesLipid raftNeuronsbiologyATP synthaseChemistryReverse Transcriptase Polymerase Chain ReactionTerpenesGeneral NeuroscienceAnticholesteremic AgentsCell MembraneMembrane ProteinsTricarboxylic AcidsZaragozic acidGeneral MedicineBridged Bicyclo Compounds HeterocyclicEnzyme ActivationPsychiatry and Mental healthClinical PsychologyADAM ProteinsCholesterolFarnesyl-Diphosphate FarnesyltransferaseBiochemistrybiology.proteinlipids (amino acids peptides and proteins)LovastatinGeriatrics and GerontologyAmyloid Precursor Protein SecretasesHydroxymethylglutaryl-CoA Reductase InhibitorsAmyloid precursor protein secretasemedicine.drugJournal of Alzheimer's disease : JAD
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Down-regulation of Endogenous Amyloid Precursor Protein Processing due to Cellular Aging

2005

Processing of amyloid precursor protein (APP) is a well acknowledged central pathogenic mechanism in Alzheimer disease. However, influences of age-associated cellular alterations on the biochemistry of APP processing have not been studied in molecular detail so far. Here, we report that processing of endogenous APP is down-regulated during the aging of normal human fibroblasts (IMR-90). The generation of intracellular APP cleavage products C99, C83, and AICD gradually declines with increasing life span and is accompanied by a reduced secretion of soluble APP (sAPP) and sAPPalpha. Further, the maturation of APP was reduced in senescent cells, which has been shown to be directly mediated by a…

ADAM10NicastrinEndogenyBiochemistryCell LineAmyloid beta-Protein PrecursorMembrane MicrodomainsDownregulation and upregulationEndopeptidasesmental disordersPresenilin-1Amyloid precursor proteinAspartic Acid EndopeptidasesHumansSecretionMolecular BiologyCellular SenescenceMembrane GlycoproteinsbiologyChemistryMembrane ProteinsCell BiologyFibroblastsCholesterolBiochemistrybiology.proteinAmyloid Precursor Protein SecretasesProtein Processing Post-TranslationalAmyloid precursor protein secretaseIntracellularJournal of Biological Chemistry
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Metabolic signatures across the full spectrum of non-alcoholic fatty liver disease.

2022

Funder: European Commission

ALTtype 2 diabetes mellitusROC receiving operator characteristicaspartate aminotransferaseHSDLDL low-density lipoproteinUHPLC ultrahigh-performance liquid chromatographyROCHCCNon-alcoholic steatohepatitisGCPCANASHGastroenterology2-HB 2-hydroxybutanoic acid; 3-HB 3-hydroxybutanoic acid; ALT alanine aminotransferase; AST aspartate aminotransferase; CE cholesterol ester; Cer ceramide; FFA free fatty acid; FLIP Fatty Liver Inhibition of Progression; Fibrosis; GC gas chromatography; HCC hepatocellular carcinoma; HSD honest significant difference; LC lipid cluster; LDL low-density lipoprotein; LM lipid and metabolite; LMC lipid metabolite and clinical variable; LPC lysophosphatidylcholine; Lipidomics; Mass spectrometry; Metabolomics; NAFL non-alcoholic fatty liver; NAFLD non-alcoholic fatty liver disease; NAS NASH activity score; NASH non-alcoholic steatohepatitis; NIDDK NASH-CRN National Institute of Digestive Diseases and Kidney NASH Clinical Research Network; NRR non-rejection rate; Non-alcoholic steatohepatitis; PC(O) ether PC; PC phosphatidylcholine; PCA principal component analysis; PE phosphatidylethanolamine; QTOFMS quadrupole-time-of-flight mass spectrometry; ROC receiving operator characteristic; SAF steatosis activity and fibrosis; SM sphingomyelin; T2DM type 2 diabetes mellitus; TG triacylglycerol; UHPLC ultrahigh-performance liquid chromatographySAFSAF steatosis activity and fibrosisLM lipid and metabolitehonest significant differenceHSD honest significant differenceTG triacylglycerolnon-rejection ratecholesterol esterPCPEGC gas chromatographyfree fatty acidFLIPNASH non-alcoholic steatohepatitisNIDDK NASH-CRN National Institute of Digestive Diseases and Kidney NASH Clinical Research NetworkBIOMARKERST2DMPE phosphatidylethanolamineLDLlipidNAFLDFFA free fatty acid2-HBMetabolomicsNAFL non-alcoholic fatty liverLMCphosphatidylcholineScience & TechnologySM sphingomyelinGastroenterology & HepatologyMass spectrometryactivitynutritional and metabolic diseasesT2DM type 2 diabetes mellitusACIDSreceiving operator characteristicdigestive system diseasesquadrupole-time-of-flight mass spectrometryLC lipid clusterlow-density lipoproteinNAS2-HB 2-hydroxybutanoic acidNAS NASH activity scoreQTOFMSether PCNRRSCORING SYSTEMprincipal component analysisgas chromatographyLC2-hydroxybutanoic acidPROGRESSIONAST aspartate aminotransferaseLMPC phosphatidylcholinePC(O)MARKERSUHPLCsteatosisTOOLImmunology and AllergyINSULIN-RESISTANCECerSMFatty Liver Inhibition of Progressionhepatocellular carcinoma2-HB 2-hydroxybutanoic acid NIDDK NASH-CRN National Institute of Digestive Diseases and Kidney NASH Clinical Research Network NRR non-rejection rate Non-alcoholic steatohepatitis PC(O) ether PC PC phosphatidylcholine PCA principal component analysis PE phosphatidylethanolamine QTOFMS quadrupole-time-of-flight mass spectrometry ROC receiving operator characteristic SAF steatosis activity and fibrosis SM T2DM type 2 diabetes mellitus TG triacylglycerol UHPLC ultrahigh-performance liquid chromatographyultrahigh-performance liquid chromatographyCELPC3-HBNAFLnon-alcoholic fatty liverTGtriacylglycerolNRR non-rejection rateLife Sciences & BiomedicineNAFLD non-alcoholic fatty liver diseaseFLIP Fatty Liver Inhibition of Progressionalanine aminotransferasemetaboliteCer ceramideCE cholesterol estersphingomyelinlysophosphatidylcholineand fibrosisALT alanine aminotransferaseInternal MedicineceramideNational Institute of Digestive Diseases and Kidney NASH Clinical Research NetworkAST3-HB 3-hydroxybutanoic acidQTOFMS quadrupole-time-of-flight mass spectrometryPCA principal component analysisLPC lysophosphatidylcholineHepatologynon-alcoholic fatty liver diseaseand clinical variablePC(O) ether PC3-hydroxybutanoic acidFibrosisNASH activity scoreNIDDK NASH-CRNlipid clusterlipid and metabolitephosphatidylethanolamineLipidomicsLMC lipid metabolite and clinical variableFFAHCC hepatocellular carcinomaJHEP reports : innovation in hepatology
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Clinical evaluation of bempedoic acid for the treatment of hyperlipidaemia.

2021

Bempedoic acid (BA) is a novel first-in-class oral lipid-lowering therapy. BA has been approved by the European Medicinal Agency and Food and Drug Administration and has been commercialised throughout Europe since the end of 2020 as an add-on therapy in patients at high/very-high cardiovascular risk that are not at LDL-C goals with current lipid-lowering treatments. Recently, Italian lipid management experts gathered to discuss several open questions on BA characteristics and BArelated practical clinical issues. The panel permitted collection of its opinions in a ten Q&A format. Aim: The aim of this viewpoint is to discuss and answer several open questions on BA characteristics and BA-r…

ATP citrate lyaseEndocrinology Diabetes and MetabolismMedicine (miscellaneous)HyperlipidemiasPharmacologyLipid-lowering therapyLipid-lowering treatmentMedicineLDL-cholesterolHumansDicarboxylic AcidsHypolipidemic AgentsLdl cholesterolNutrition and DieteticsLipid managementbusiness.industryNovel LDL-C treatment.Fatty AcidsCholesterol LDLBempedoic acidNovel LDL-C treatmentATP citrate lyaseATP citrate lyase; bempedoic acid; LDL-cholesterol; lipid-lowering treatment; novel LDL-C treatmentLipid loweringCardiology and Cardiovascular MedicinebusinessClinical evaluationBempedoic acidNutrition, metabolism, and cardiovascular diseases : NMCD
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Binding mode analysis of ABCA7 for the prediction of novel Alzheimer's disease therapeutics

2021

Graphical abstract

ATP Adenosine-triphosphateNBD nucleotide binding domainGSH reduced glutathionePolypharmacologyAlzheimer’s disease (AD)ATP-binding cassette transporterHTS high-throughput screeningBiochemistryABCA7Structural BiologyPLIF protein ligand interactionMSD membrane spanning domainPDB protein data bankTM transmembrane helixABC ATP-binding cassetteMultitarget modulation (PANABC)RMSD root mean square distanceABC transporter (ABCA1 ABCA4 ABCA7)Computer Science ApplicationsMOE Molecular Operating EnvironmentPharmacophoreSNP single-nucleotide polymorphismBiotechnologyResearch ArticleBBB blood-brain barrierBiophysicsDrug designComputational biologyBiologyAD Alzheimer’s diseasePET positron emission tomographyIC intracellular helixAPP amyloid precursor proteincryo-EM cryogenic-electron microscopyGeneticsHomology modelingBinding siteRational drug design and developmentComputingMethodologies_COMPUTERGRAPHICSNBD-cholesterol 7-nitro-2-13-benzoxadiazol-4-yl-cholesterolTransporterPSO particle swarm optimizationPET tracer (PETABC)ECD extracellular domainR-domain/region regulatory domain/regionABCA1biology.proteinEH extracellular helixTP248.13-248.65BODIPY-cholesterol 44-difluoro-4-bora-3a4a-diaza-s-indacene-cholesterolComputational and Structural Biotechnology Journal
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HETEROGENITY OF AUTOSOMAL DOMINANT HYPERCHOLESTEROLEMIA IN SICILY

2004

AUTOSOMAL DOMINANT HYPERCHOLESTEROLEMIAMUTATIONSEPIDEMIOLOGY
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IMPROVE-IT: what have we learned?

2016

Purpose of review: Recent studies and dyslipidemia treatment guidelines indicate that combination lipid-lowering therapy is frequently needed and its use has increased in recent years. Ezetimibe and simvastatin as a fixed dose is an efficacious treatment choice based on positive results of the recent IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT). In this review, we discuss recent controversies surrounding ezetimibe and provide clinical perspective on the results of the IMPROVE-IT study. Recent findings: IMPROVE-IT is the first trial that demonstrates a significant clinical benefit of a nonstatin hypolipidemic agent (ezetimibe) used in combination with sta…

Acute coronary syndromeSimvastatinHypercholesterolemia030204 cardiovascular system & hematologyPharmacologyFixed dose03 medical and health scienceschemistry.chemical_compound0302 clinical medicinePharmacotherapyEzetimibeMedicineHumansLow-density lipoprotein cholesterol030212 general & internal medicineAcute Coronary SyndromeIMPROVE-IT trialbusiness.industryCholesterolAnticholesteremic AgentsAnticholesteremic Agentsnutritional and metabolic diseasesCholesterol LDLmedicine.diseaseCardiovascular riskEzetimibeTreatment OutcomechemistrySimvastatinAzetidinesDrug Therapy CombinationHydroxymethylglutaryl-CoA Reductase InhibitorsbusinessCardiology and Cardiovascular MedicineDyslipidemiamedicine.drugCurrent opinion in cardiology
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Pharmacological Interventions on Asymmetric Dimethylarginine, a Clinical Marker of Vascular Disease

2011

The aim of this paper is to review the latest data on the pharmacological modulation of asymmetric dimethylarginine in human disease. When the terminal nitrogens of the guanidine portion of an arginine become methylated through the action of N-methyl transferases, two chemically close, but physiologically different amino acids are synthesized: symmetric and asymmetric dimethylarginine. The vascular origin of asymmetric dimethylarginine and its inhibitory activity on endothelial nitric oxide synthase give it an important role in certain diseases in which microcirculation is compromised: hypertension, atherosclerosis, inflammatory bowel disease, and diabetes. This review discusses the role th…

Adrenergic Antagonistsmedicine.medical_specialtyAngiotensinsNitric Oxide Synthase Type IIIArginineHypercholesterolemiaPeroxisome Proliferator-Activated ReceptorsHyperhomocysteinemiaReceptors Cytoplasmic and NuclearPeroxisome proliferator-activated receptorPharmacologyArginineBiochemistryNitric oxideDiabetes Complicationschemistry.chemical_compoundInternal medicineDrug DiscoveryAdrenergic antagonistmedicineHumansVascular DiseasesPharmacologychemistry.chemical_classificationVascular diseaseMicrocirculationOrganic Chemistrymedicine.diseaseAngiotensin IIEndocrinologychemistryHypertensionMolecular MedicineKidney DiseasesFarnesoid X receptorHydroxymethylglutaryl-CoA Reductase InhibitorsAsymmetric dimethylarginineCurrent Medicinal Chemistry
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Homozygous familial hypercholesterolemia in Italy: Clinical and molecular features

2020

Abstract Background and aims Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by extremely elevated plasma levels of low density lipoprotein cholesterol (LDL-C) and high risk of premature atherosclerotic cardiovascular disease (ASCVD). HoFH is caused by pathogenic variants in several genes, such as LDLR, APOB and PCSK9, responsible for autosomal dominant hypercholesterolemia (ADH), and LDLRAP1 responsible for autosomal recessive hypercholesterolemia (ARH). Aim of this study was the review of the clinical and molecular features of patients with HoFH identified in Italy from 1989 to 2019. Methods Data were collected from lipid clinics and laboratories, …

Adult0301 basic medicinemedicine.medical_specialtyCandidate geneCandidate geneGenotype-phenotype correlationApolipoprotein BCandidate genes; Genotype-phenotype correlations; Homozygous familial hypercholesterolemia; Pathogenic variantsHomozygous familial hypercholesterolemiaGenotype-phenotype correlationsFamilial hypercholesterolemia030204 cardiovascular system & hematologyCompound heterozygosityCandidate genesHyperlipoproteinemia Type II03 medical and health sciences0302 clinical medicineInternal medicinemedicineHumansbiologybusiness.industryPCSK9HomozygoteGenetic disorderPathogenic variantsCandidate genes; Genotype-phenotype correlations; Homozygous familial hypercholesterolemia; Pathogenic variants;medicine.diseasePhenotype030104 developmental biologyEndocrinologyItalyReceptors LDLAutosomal Recessive HypercholesterolemiaMutationLDL receptorbiology.proteinlipids (amino acids peptides and proteins)Proprotein Convertase 9Cardiology and Cardiovascular Medicinebusiness
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Influence of LDL receptor gene mutations and the R3500Q mutation of the apoB gene on lipoprotein phenotype of familial hypercholesterolemic patients …

2003

Few data are available on genotype-phenotype interactions among familial hypercholesterolemia (FH) patients in South European populations and there are no data about the influence of R3500Q mutation on lipoprotein phenotype compared to low-density lipoprotein receptor (LDLR) mutations. The objective of the study is to analyze the influence of mutations in the LDLR and apolipoprotein B (apoB) genes on lipoprotein phenotype among subjects clinically diagnosed of FH living in East Spain. In all, 113 FH index patients and 100 affected relatives were studied. Genetic diagnosis was carried out following a protocol based on Southern blot and PCR-SSCP analysis. A total of 118 FH subjects could be c…

AdultAdolescentApolipoprotein BHypercholesterolemiaPopulationMutation MissenseFamilial hypercholesterolemiaBiologymedicine.disease_causechemistry.chemical_compoundGeneticsmedicineHumansMissense mutationeducationGenetics (clinical)Apolipoproteins BGeneticsMutationeducation.field_of_studyCholesterolMiddle Agedmedicine.diseaseEuropePhenotypeReceptors LDLchemistryLDL receptorbiology.proteinlipids (amino acids peptides and proteins)LipoproteinEuropean Journal of Human Genetics
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