Therapeutic Potential of FGF21 for Alzheimer’s Disease
FGF21 对阿尔茨海默病的治疗潜力
基本信息
- 批准号:10740063
- 负责人:
- 金额:$ 59.07万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-15 至 2028-05-31
- 项目状态:未结题
- 来源:
- 关键词:3xTg-AD mouseAffectAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAlzheimer&aposs disease riskAlzheimer&aposs disease therapyAnimal ModelAttenuatedBackBody Weight decreasedBrainBrain DiseasesBrain regionCellsCentral Nervous SystemClinical TrialsCognitionCognitive agingCytoprotectionDataDefectDementiaDiabetes MellitusDiseaseDisease ProgressionDissectionEndocrineFGFR1 geneFatty acid glycerol estersFibroblast Growth Factor ReceptorsGLUT 4 proteinGenesGeneticGlycoproteinsHippocampusHomeostasisHormonesHumanImpaired cognitionImpairmentIn VitroInsulinKnock-outKnowledgeLearningLife ExpectancyLiverLong-Term PotentiationMediatingMemoryMemory impairmentMetabolicMetabolic DiseasesMetabolic PathwayMetabolic dysfunctionMetabolismMitochondriaModelingMusNerve DegenerationNeurodegenerative DisordersNeuronal PlasticityNeuronsObesityOxidative StressPathologicPathway interactionsPeripheralPhysiologicalPhysiological ProcessesPhysiologyPlayPublishingRodentRoleSignal TransductionSliceSpecificityStressSymptomsTechniquesThalamic structureTherapeuticTissuesUp-RegulationVertebral columnWild Type MouseWorkabeta accumulationblood glucose regulationcholinergic neuroncognitive functioncomorbidityeffective therapyfibroblast growth factor 21glucose metabolismhyperphosphorylated tauimprovedin vivoinnovationinsulin sensitivityinsulin signalingmetabolic profilemetabolomicsmimeticsmitochondrial dysfunctionmouse modelneuronal metabolismneuroprotectionneurotransmissionnonhuman primatenovelnovel strategiespharmacologicpreventreceptorreduce symptomsresponsespatial memorysymptomatic improvementway finding
项目摘要
Project Summary / Abstract
Cognitive dysfunction and dementia rates are increasing worldwide in part due to the significant increase
in life expectancy. Alzheimer’s disease (AD), the main cause of dementia, is a progressive
neurodegenerative brain disease characterized by impairments in cognitive function. Aging is the main risk
factor for AD and unfortunately there is no effective treatment for slowing down aging or treating AD.
Current approaches to treat AD (e.g., amyloid beta accumulation and tau hyperphosphorylation) have been
unsuccessful which calls for novel approaches to treat the full spectrum of this disease. Recent studies
have postulated that cognitive decline and AD might be manifestations of metabolic disorders. In particular,
changes in glucose metabolism and brain insulin sensitivity have been identified as common features
observed in AD. Our published works reveal that the endocrine hormone fibroblast growth factor 21
(FGF21) decreases body weight during obesity, improves insulin sensitivity, and corrects metabolic
dysfunctions in animal models. Clinical trials with FGF21 mimetics have also demonstrated the efficacy of
targeting this pathway to improve metabolic profiles in humans. Interestingly, recent data suggests that
FGF21 administration may also prevent neurodegeneration and pathological deficits in animal models of
AD. While circulating FGF21 levels are derived primarily by the liver, our recently published study reveals
the unexpected discovery that FGF21 is also expressed in a very specific region of the central nervous
system. Specifically, FGF21 is expressed in the retrosplenial cortex and can signal to the hippocampus
and can regulate learning and memory. A previous study demonstrates that FGF21 is induced from
neurons in response to mitochondrial stress. These observations are the backbone of our main hypothesis
in this proposal which seeks to interrogate whether FGF21 signals to neurons in hippocampus to not only
improve neuronal metabolism and memory, but also improves AD symptoms. This proposal employs
various genetic AD mouse models to explore different aspects of AD, as well as genetic and
pharmacological approaches, to investigate the effects of FGF21 and in the improvement of memory and
cognition. Together, these studies will not only further our knowledge of the role of FGF21 in neuronal
metabolism but will also provide a better understanding of potential metabolic abnormalities during AD.
Finally, these studies may reveal a potential therapeutic approach to treat AD and its related dementias.
项目摘要/摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Matthew Joseph Potthoff其他文献
Matthew Joseph Potthoff的其他文献
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{{ truncateString('Matthew Joseph Potthoff', 18)}}的其他基金
Central Mechanisms Regulating Macronutrient Intake
调节大量营养素摄入的中心机制
- 批准号:
10266052 - 财政年份:2019
- 资助金额:
$ 59.07万 - 项目类别:
Central Mechanisms Regulating Macronutrient Intake
调节大量营养素摄入的中心机制
- 批准号:
9974289 - 财政年份:2019
- 资助金额:
$ 59.07万 - 项目类别:
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