Aberrant Circadian Regulation of Autophagy in the Heart During Diabetes
Aberrant Circadian Regulation of Autophagy in the Heart During Diabetes
批准号:
10288158
负责人:
JOHN C CHATHAM
金额:
$37.13万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-04-15 至 2023-01-31
关键词:
AddressAdministrative SupplementAdverse effectsAffectAgeAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease patientAlzheimer&aposs disease riskAnimal ModelAnimalsAutophagocytosisAwardBiochemicalBioenergeticsBiologicalBiologyBrainCell modelCircadian DysregulationClinicalCognitionCognitiveDataDefectDegradation PathwayDementiaDiabetes MellitusDrowsinessElderlyElectron TransportEpidemiologyGeneticGoalsGrantHeartHistologyHumanImpaired cognitionImpairmentInterventionLinkMetabolicMetabolic dysfunctionMetabolismMethodsMitochondriaMyocardial dysfunctionNerve DegenerationNervous System PhysiologyNeurodegenerative DisordersNeurologicNeuronsNon-Insulin-Dependent Diabetes MellitusParentsPathogenesisPathologicPathologyPathway interactionsPatientsPharmacologyPhenotypePlayPositioning AttributePost-Translational Protein ProcessingProteinsProtocols documentationQuality ControlRegulationRiskRoleSeveritiesSleepSleep Wake CycleSolidSymptomsTestingTissuesUnited States National Institutes of Healthage relatedcircadiancircadian pacemakercircadian regulationcognitive functioncomorbiditydiabeticdiabetic cardiomyopathyexperiencegenetic manipulationglucose metabolismhuman old age (65+)in vivoinnovationinsightinsulin sensitivitylipid metabolismmitochondrial DNA mutationmitochondrial autophagymitochondrial dysfunctionmouse geneticsneuropathologyparent projectprotein aggregationresponsesleep regulation
中文摘要
本行政补充是对标题为“以阿尔茨海默氏症为重点的行政管理”的NOT-AG-20-034的回应
英文摘要
This Administrative Supplement is in response to NOT-AG-20-034, entitled ‘Alzheimer’s-focused administrative
supplements for NIH grants that are not focused on Alzheimer’s disease’. The overall goal of this supplement
is to use our existing award, focused on how diabetes-dependent disruption of the circadian clock contributes
to the adverse effects of diabetes on the heart, as the platform to assess the impact of these factors on
Alzheimer’s disease (AD) and its related dementias (ADRD). The parent application tests the hypothesis that
changes in the modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc) during diabetes impairs
circadian regulation of autophagy/mitophagy in cardiac dysfunction. Interestingly, circadian dysregulation,
diabetes, perturbation of protein O-GlcNAcylation, mitochondrial dysfunction and autophagy/mitophagy have
also all been linked to AD. It is currently unknown whether 1) O-GlcNAcylation, mitophagy, and mitochondrial
function in the brain are circadian regulated and affected by diabetes; and 2) whether circadian, O-GlcNAc and
mitophagy manipulations change cognition and neuropathology. Thus our current supplement application will
test the hypothesis that AD and ADRD related neurological and pathological phenotypes are a
consequence of dysregulation of the circadian clock-O-GlcNAcylation axis resulting in impaired
neuronal mitophagy and bioenergetics that is exacerbated by T2DM. The same mouse genetic and
pharmacological manipulations, parallel histology and biochemical methods will be used in the brain
in the supplement project, as described in the parent project. We will perform studies with the
following 2 aims: 1) Determine whether the circadian regulation of O-GlcNAcylation, mitophagy and
mitochondrial function in the brain, as well as cognition and neuropathology, are affected by diabetes; and 2)
Determine whether genetic perturbation of mitophagy, pharmacological enhancement of mitophagy, and
pharmacological perturbation of circadian clock affect O-GlcNAcylation, mitophagy, mitochondrial function,
cognition and neuropathology. The goal is to gain new fundamental insights into aspects of circadian disruption
and diabetes in the pathogenesis of AD, which have not been investigated previously. New insights gained
from this study will help identify innovative approaches for alleviating cognitive and neuropathological deficits in
AD.
期刊论文(4)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1016/j.coph.2020.08.005
发表时间:
2021-04
期刊:
Current opinion in pharmacology
影响因子:
4
作者:
[]
通讯作者:
The role of protein O-linked N-Acetylglucosamine in regulating cardiac physiology
-
批准号:10213829
-
项目类别:
-
资助金额:$18.56万
-
财政年份:2020
-
负责人:JOHN C CHATHAM
-
依托单位:
STIM1 and its role in regulating cardiac metabolism
-
批准号:10371868
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项目类别:
-
资助金额:$54.66万
-
财政年份:2020
-
负责人:JOHN C CHATHAM
-
依托单位:
STIM1 and its role in regulating cardiac metabolism
-
批准号:10592268
-
项目类别:
-
资助金额:$54.66万
-
财政年份:2020
-
负责人:JOHN C CHATHAM
-
依托单位:
Circadian regulation of vascular aging
-
批准号:10323289
-
项目类别:
-
资助金额:$62.84万
-
财政年份:2019
-
负责人:JOHN C CHATHAM
-
依托单位:
Circadian regulation of vascular aging
-
批准号:10094243
-
项目类别:
-
资助金额:$62.84万
-
财政年份:2019
-
负责人:JOHN C CHATHAM
-
依托单位:
Administrative Supplement to Award "Circadian regulation of vascular aging"
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批准号:10283788
-
项目类别:
-
资助金额:$37.13万
-
财政年份:2019
-
负责人:JOHN C CHATHAM
-
依托单位:
Rapid modulation of hippocampal GABAergic Inhibition by O-GlcNAcylation
-
批准号:9765783
-
项目类别:
-
资助金额:$40.84万
-
财政年份:2019
-
负责人:JOHN C CHATHAM
-
依托单位:
Aberrant Circadian Regulation of Autophagy in the Heart During Diabetes
-
批准号:9543678
-
项目类别:
-
资助金额:$48.11万
-
财政年份:2018
-
负责人:JOHN C CHATHAM
-
依托单位:
Aberrant Circadian Regulation of Autophagy in the Heart During Diabetes
-
批准号:10078980
-
项目类别:
-
资助金额:$48.11万
-
财政年份:2018
-
负责人:JOHN C CHATHAM
-
依托单位:
Disruption of the Clock O-GlcNAc axis in diabetic cardiomyopathy
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批准号:8814019
-
项目类别:
-
资助金额:$36.75万
-
财政年份:2014
-
负责人:JOHN C CHATHAM
-
依托单位:
Disruption of the Clock O-GlcNAc axis in diabetic cardiomyopathy
-
批准号:8960945
-
项目类别:
-
资助金额:$36.75万
-
财政年份:2014
-
负责人:JOHN C CHATHAM
-
依托单位:
Disruption of the Clock O-GlcNAc axis in diabetic cardiomyopathy
-
批准号:9172241
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项目类别:
-
资助金额:$36.75万
-
财政年份:2014
-
负责人:JOHN C CHATHAM
-
依托单位:
STIM1 mediated calcium entry: A new paradigm of metabolic regulation of cardiomyo
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批准号:8459907
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项目类别:
-
资助金额:$17.55万
-
财政年份:2012
-
负责人:JOHN C CHATHAM
-
依托单位:
STIM1 mediated calcium entry: A new paradigm of metabolic regulation of cardiomyo
-
批准号:8308227
-
项目类别:
-
资助金额:$23.16万
-
财政年份:2012
-
负责人:JOHN C CHATHAM
-
依托单位:
O-GlcNAcylation and Hippocampal Synaptic Plasticity
-
批准号:8206266
-
项目类别:
-
资助金额:$32.05万
-
财政年份:2011
-
负责人:JOHN C CHATHAM
-
依托单位:
O-GlcNAcylation and Hippocampal Synaptic Plasticity
-
批准号:8675760
-
项目类别:
-
资助金额:$31.73万
-
财政年份:2011
-
负责人:JOHN C CHATHAM
-
依托单位:
O-GlcNAcylation and Hippocampal Synaptic Plasticity
-
批准号:8484465
-
项目类别:
-
资助金额:$30.93万
-
财政年份:2011
-
负责人:JOHN C CHATHAM
-
依托单位:
O-GlcNAcylation and Hippocampal Synaptic Plasticity
-
批准号:8269637
-
项目类别:
-
资助金额:$32.05万
-
财政年份:2011
-
负责人:JOHN C CHATHAM
-
依托单位:
Protein O-GlcNAcylation and the regulation of cardiac function
-
批准号:7998729
-
项目类别:
-
资助金额:$36.63万
-
财政年份:2010
-
负责人:JOHN C CHATHAM
-
依托单位:
Protein O-GlcNAcylation and the regulation of cardiac function
-
批准号:8656250
-
项目类别:
-
资助金额:$5.27万
-
财政年份:2010
-
负责人:JOHN C CHATHAM
-
依托单位:
海外基金