0000000000324047

AUTHOR

Luca Caruana

showing 5 related works from this author

Insulin resistance as common molecular denominator linking obesity to Alzheimer’s disease

2015

Alzheimer’s disease (AD) is an aging-related multi-factorial disorder to which metabolic factors contribute at what has canonically been considered a centrally mediated process. Although the exact underlying mechanisms are still unknown, obesity is recognized as a risk factor for AD and the condition of insulin resistance seems to be the link between the two pathologies. Using mice with high fat diet (HFD) obesity we dissected the molecular mechanisms shared by the two disorders. Brains of HFD fed mice showed elevated levels of APP and Aβ 40 /Aβ 42 together with BACE, GSK3β and Tau proteins involved in APP processing and Aβ accumulation. Immunofluorescence, Thioflavin T staining experiments…

Malemedicine.medical_specialtyTime FactorsAdipokineAmyloidogenic ProteinsInflammationBiologyDiet High-Fatmedicine.disease_causeAdipokines Alzheimer’s disease gene expression inflammation insulin resistance mitochondrial dysfunction obesity.Settore BIO/09 - FisiologiaGlycogen Synthase Kinase 3MiceInsulin resistanceAlzheimer DiseaseInternal medicinemedicineAnimalsInsulinObesityReceptorGSK3BGlycogen Synthase Kinase 3 betaSettore BIO/16 - Anatomia UmanaNeurodegenerationBrainmedicine.diseaseReceptor InsulinMice Inbred C57BLDisease Models AnimalOxidative StressInsulin receptorEndocrinologyGene Expression RegulationNeurologyCase-Control Studiesbiology.proteinCytokinesNeurology (clinical)Amyloid Precursor Protein SecretasesInsulin Resistancemedicine.symptomOxidative stressSignal Transduction
researchProduct

Altered insulin pathway compromises mitochondrial function and quality control both in in vitro and in vivo model systems.

2021

Abstract Altered insulin signaling and insulin resistance are considered the link between Alzheimer's disease (AD) and metabolic syndrome. Here, by using an in vitro and an in vivo model, we investigated the relationship between these disorders focusing on neuronal mitochondrial dysfunction and mitophagy. In vitro Aβ insult induced the opening of mitochondrial permeability transition pore (mPTP), mitochondrial membrane potential (ΔΨm) loss, and apoptosis while insulin addition ameliorated these dysfunctions. The same alterations were detected in a 16 weeks of age mouse model of diet-induced obesity and insulin resistance. In addition, we detected an increase of fission related proteins and …

MaleAgingAmyloid beta-Peptidemedicine.medical_treatmentMetabolic diseasePINK1Insulin pathway Neurodegeneration Metabolic diseases Mitochondrion Mitophagy AgingMitochondrionDiet High-FatParkinNOMiceInsulin resistanceMetabolic DiseasesCell Line TumorMitophagymedicineAnimalsHumansInsulinMitochondrionNeurodegenerationMolecular BiologyAmyloid beta-PeptidesbiologyAnimalChemistryInsulinMitophagyCell Biologymedicine.diseaseCell biologyMitochondriaMice Inbred C57BLInsulin receptorMitochondrial permeability transition porebiology.proteinMolecular MedicineInsulin ResistanceInsulin pathwayHumanSignal TransductionMitochondrion
researchProduct

Metformin increases APP expression and processing via oxidative stress, mitochondrial dysfunction and NF-κB activation: Use of insulin to attenuate m…

2015

AbstractClinical and experimental biomedical studies have shown Type 2 diabetes mellitus (T2DM) to be a risk factor for the development of Alzheimer's disease (AD). This study demonstrates the effect of metformin, a therapeutic biguanide administered for T2DM therapy, on β-amyloid precursor protein (APP) metabolism in in vitro, ex vivo and in vivo models. Furthermore, the protective role of insulin against metformin is also demonstrated. In LAN5 neuroblastoma cells, metformin increases APP and presenilin levels, proteins involved in AD. Overexpression of APP and presenilin 1 (Pres 1) increases APP cleavage and intracellular accumulation of β-amyloid peptide (Aβ), which, in turn, promotes ag…

Maleendocrine system diseasesmedicine.medical_treatmentmedicine.disease_causeAntioxidantsNF-κBAmyloid beta-Protein PrecursorAspartic Acid EndopeptidasesInsulinBiguanideNF-kappa BBrainAlzheimer's diseaseMetforminMetforminMitochondriaProtein TransportAntioxidantmedicine.drugmetformin T2DM Alzheimer's diseaseAdultmedicine.medical_specialtyProgrammed cell deathmedicine.drug_classOxidative phosphorylationBiologyAntidiabetic drugModels BiologicalPresenilinInternal medicineCell Line Tumormental disordersmedicinePresenilin-1AnimalsHumansMolecular BiologyCell NucleusSettore MED/04 - Patologia GeneraleAmyloid beta-PeptidesInsulinAdenylate KinaseOxidative Stress Pathwaynutritional and metabolic diseasesCell BiologyHydrogen PeroxideMice Inbred C57BLEndocrinologyGene Expression RegulationCytoprotectionOxidative stressLeukocytes MononuclearAmyloid Precursor Protein SecretasesOxidative stressBiochimica et Biophysica Acta (BBA) - Molecular Cell Research
researchProduct

Biological and biophysics aspects of metformin-induced effects: cortex mitochondrial dysfunction and promotion of toxic amyloid pre-fibrillar aggrega…

2016

The onset of Alzheimer disease (AD) is influenced by several risk factors comprising diabetes. Within this context, antidiabetic drugs, including metformin, are investigated for their effect on AD. We report that in the C57B6/J mice, metformin is delivered to the brain where activates AMP-activated kinase (AMPK), its molecular target. This drug affects the levels of β- secretase (BACE1) and β-amyloid precursor protein (APP), promoting processing and aggregation of β-amyloid (Aβ), mainly in the cortex region. Moreover, metformin induces mitochondrial dysfunction and cell death by affecting the level and conformation of Translocase of the Outer Membrane 40 (TOM40), voltage-dependent anion-sel…

0301 basic medicineAgingmedicine.medical_specialtyMitochondrial poreAmyloidTranslocase of the outer membraneContext (language use)AMP-Activated Protein KinasesBiologyAmyloid beta-Protein PrecursorMice03 medical and health sciences0302 clinical medicineβ-amyloid aggregationAlzheimer DiseaseHexokinaseInternal medicine?-amyloid aggregationmitochondrial dysfunctionmedicineAnimalsHypoglycemic Agentsmitochondrial poresMitochondrial transportAmyloid beta-PeptidesVoltage-Dependent Anion Channel 1BrainAMPKcell degenerationCell BiologyAlzheimer's diseasemedicine.diseaseMitochondriaMetformin030104 developmental biologyEndocrinologyAmyloid Precursor Protein SecretasesAlzheimer's diseasemetforminVDAC1030217 neurology & neurosurgeryResearch Papermedicine.drug
researchProduct

Inflammatory mediators as biomarkers in brain disorders.

2013

Neurodegenerative diseases such as Alzheimer, Parkinson, amyotrophic lateral sclerosis, and Huntington are incurable and debilitating conditions that result in progressive death of the neurons. The definite diagnosis of a neurodegenerative disorder is disadvantaged by the difficulty in obtaining biopsies and thereby to validate the clinical diagnosis with pathological results. Biomarkers are valuable indicators for detecting different phases of a disease such as prevention, early onset, treatment, progression, and monitoring the effect of pharmacological responses to a therapeutic intervention. Inflammation occurs in neurodegenerative diseases, and identification and validation of molecules…

medicine.medical_specialtyPathologyImmunologyPopulationInflammationDiseaseBioinformaticsInternal medicinemedicineImmunology and AllergyHumansAmyotrophic lateral sclerosiseducationPathologicalSettore MED/04 - Patologia Generaleeducation.field_of_studyInflammation biomarkersbusiness.industryNeurodegenerative Diseasesmedicine.diseaseRheumatologyinflammationmedicine.symptomAlzheimer's diseaseInflammation MediatorsbusinessBiomarkers
researchProduct