Cognitive dysfunction and Metabolic DisorderFattyAcidGlucosCYTOPLASMLipolysisI.GlucoseMetabolisminADAcetyl-CoAATPLipogenesisLA.GlucoseuptakedeficitGlycolysisB.InsulinresistanceoPyruvateC. GlycosylationH,OATP?Acetyl-CoAOHeH202TCACycleADPI.Lipid MetabolisminAD?AcetoacetateeA.LipiddysregulationasanearlysignalKetogenesisRespirationB.LipogenesisC. LipolysisNADHFADHβ-HBAcetoneD.Hepatic inflammatoryfactorCYTOPLASMMITOCHONDRIAenhancesketogenesisCOAlternativeenergyfuelUnpublishedIll.MitochondriaattheCoreofMetabolisminADA.MitochondrialdysfunctionprecedesmetabolicdisorderB.Mitochondria mediate pathologic impairment during AD progressionC.Mitochondrial remodelingD.Mitochondria-launched inflammation and oxidative stress during thepathogenesisE.Mitochondrial metabolic disorder links nutritional imbalance to neural DNA epigenetic remodeling
Cognitive dysfunction and Metabolic Disorder I. Glucose Metabolism in AD A. Glucose uptake deficit B. Insulin resistance C. Glycosylation II. Lipid Metabolism in AD A. Lipid dysregulation as an early signal B. Lipogenesis C. Lipolysis D. Hepatic inflammatory factor enhances ketogenesis III. Mitochondria at the Core of Metabolism in AD A. Mitochondrial dysfunction precedes metabolic disorder B. Mitochondria mediate pathologic impairment during AD progression C. Mitochondrial remodeling D. Mitochondria-launched inflammation and oxidative stress during the pathogenesis E. Mitochondrial metabolic disorder links nutritional imbalance to neural DNA epigenetic remodeling Unpublished
西安交通大学ResearchStrategiesXIANJIAOTONGUNIVERSITYMonitoringtimecourse of pathogenesisMultiomicsstudyonMitochondriafunctionClinical biopsyInvitro&InvivomodelsMitochondriadynamics&metabolomicsstudy20002500300Beneficial effectsTime (s)MitochondrialBiomarkers&Biochemistry&Molecularoncognition&therapeutichomoestasisbiology&FunctionalmetabolismtargetsanalysisNutrients.NaturalproductsMedicineMolecularscreenandintervention
Mitochondria dynamics & metabolomics study Biochemistry & Molecular biology& Functional analysis Biomarkers & therapeutic targets Nutrients, Natural products, Medicine Mitochondrial homoestasis Multiomics study on Mitochondria function Beneficial effects on cognition & metabolism Clinical biopsy In vitro & In vivo models Monitoring time course of pathogenesis Molecular screen and intervention Research Strategies
Points to be addressed: Hyperglycemia- induced neuronal mitochondrialdysfunction and insulin resistance: Peripheral lipid/glucose metabolic remodeling inAPP/ps1 mouse: Biomarkers for early diagnosisofAD: Target mitochondria by mitochondrial nutrients:Hydroxytyrosol and Hydrogen
Points to be addressed • Hyperglycemia- induced neuronal mitochondrial dysfunction and insulin resistance • Peripheral lipid/glucose metabolic remodeling in APP/PS1 mouse: Biomarkers for early diagnosis of AD • Target mitochondria by mitochondrial nutrients: Hydroxytyrosol and Hydrogen
Impaired Insulin Signaling/Mt dysfunction in AD Brain(postmortem samples)NDADNDADNDADNDMCI=150AKTADGSK-3αsaruerojo%GSK-3β100p70S6KActin50-eee1IVMDH100NDAD50-AKTGSK-3aGSK-3βp70JiangangLong,etal.JournalofAlzheimer'sDisease,2012
Impaired Insulin Signaling/Mt dysfunction in AD Brain （postmortem samples) + * + + ++ ** * Jiangang Long, et al. Journal of Alzheimer's Disease, 2012
Mitochondrialdysfunctionprecedesinsulinresistanceinneurondegeneration underhyperglycemiaHighGlucoseMtdysfunctionP-AMPK/AKTMtcomponentlossInsulinresistanceNeuronal ImpairmentandMetabolicDisorderYunhuaPeng,etal.JournalofNeurochemistry,2016
Neuronal Impairment and Metabolic Disorder High Glucose p-AMPK/AKT ↓ Mt dysfunction Mt component loss Insulin resistance Mitochondrial dysfunction precedes insulin resistance in neuron degeneration under hyperglycemia Yunhua Peng, et al. Journal of Neurochemistry, 2016