Pharmacologic Inhibition of PDE11A for Age-Related Memory Disorders
Pharmacologic Inhibition of PDE11A for Age-Related Memory Disorders
批准号:
10401488
负责人:
CHARLES S. HOFFMAN
金额:
$73.15万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
未结题
起止时间:
2020-09-15 至 2025-04-30
关键词:
AcuteAddressAdverse eventAgeAge-Related Memory DisordersAge-associated memory impairmentAgingAnimal ModelAnimalsAnteriorAnxietyAreaAttentionBehaviorBehavioralBiological AssayBrainBrain regionCellsControlled StudyCyclic AMPCyclic GMPDataDementiaDiseaseDisease modelDoseDrug KineticsDrug TargetingEnzymesEvaluationFamilyGenesGeneticHealthHippocampal FormationHippocampus (Brain)HumanImpaired cognitionIn VitroInvestigationKnock-outLeadLibrariesLiteratureMammalian CellMeasuresMediatingMemoryMemory LossMemory impairmentMental DepressionMental disordersMethodsMotorMotor ActivityMusMutant Strains MiceNeurodegenerative DisordersNeuronsOralPerformancePermeabilityPharmacologyPhosphorylationPhysiologicalPrimatesProtein IsoformsProteinsResearchRodentSensorySignal TransductionSignaling MoleculeSocial BehaviorSocial InteractionSystemViralYeastsage relatedagedanalogbasebehavioral studycohortdementedeffective therapyenzyme substrateexperimental studyimprovedin vivoin vivo Modelinhibitorinnovationlong term memorymemory retrievalmouse modelnovelnovel therapeutic interventionpharmacokinetics and pharmacodynamicsphosphodiesterase 11apreventscreeningside effectsmall moleculesmall molecule inhibitortherapeutic target
中文摘要
项目总结
英文摘要
Project Summary
Age-related loss of memory remains a disease for which there are no effective treatments.
Data suggests that an enzyme found in a specific region of the brain associated with memory,
phosphodiesterase 11A (PDE11A), is increasingly expressed as humans age, and that levels of
key signaling molecules in the brain that are substrates for this enzyme decrease in tandem,
leading to the hypothesis that PDE11A is directly responsible for this effect. Our experiments with
mice lacking PDE11A revealed that these animals behave and reproduce normally and do not
suffer from the same age related loss of memory as their wild type littermates. This data
collectively leads to the hypothesis that PDE11A may be a valuable target for study as a means
to treat age-related loss of memory.
There are no known potent and selective PDE11A inhibitors. A number of other PDE
enzymes are under investigation or have been studied for various psychiatric and
neurodegenerative diseases, indicating that this family can be targeted by small molecules. A
novel screening method using yeast that express human PDE11A identified a number of good
starting points. Some of these hits demonstrated excellent selectivity for PDE11A with the
potential to be optimized to provide the first potent, selective PDE11A inhibitors with a profile that
will allow us to investigate these compounds in mouse models of age-related behavior and
memory.
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会议论文
Pharmacologic Inhibition of PDE11A for Age-Related Memory Disorders
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批准号:10260396
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项目类别:
-
资助金额:$73.78万
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财政年份:2020
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负责人:CHARLES S. HOFFMAN
-
依托单位:
Pharmacologic Inhibition of PDE11A for Age-Related Memory Disorders
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批准号:10617261
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项目类别:
-
资助金额:$72.6万
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财政年份:2020
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负责人:CHARLES S. HOFFMAN
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依托单位:
An in vivo screen for biological and chemical regulators of mammalial PDEs
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批准号:7337165
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项目类别:
-
资助金额:$19.43万
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财政年份:2007
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负责人:CHARLES S. HOFFMAN
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依托单位:
ADENYLATE CYCLASE-ASSOCIATED COMPLEXES IN SCHIZOSACCHAROMYCES POMBE
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批准号:7602230
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项目类别:
-
资助金额:$0.62万
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财政年份:2007
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负责人:CHARLES S. HOFFMAN
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依托单位:
An in vivo screen for biological and chemical regulators of mammalial PDEs
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批准号:7187461
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项目类别:
-
资助金额:$23.29万
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财政年份:2007
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负责人:CHARLES S. HOFFMAN
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依托单位:
ADENYLATE CYCLASE-ASSOCIATE COMPLEXES IN SCHIZOSACCHAROMYCES POMBE
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批准号:7420704
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项目类别:
-
资助金额:$0.29万
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财政年份:2006
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负责人:CHARLES S. HOFFMAN
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依托单位:
ADENYLATE CYCLASE-ASSOCIATE COMPLEXES IN S. POMBE
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批准号:6979642
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项目类别:
-
资助金额:$0.36万
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财政年份:2004
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负责人:CHARLES S. HOFFMAN
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依托单位:
CHARACTERIZATION OF THE S POMBE CAMP SIGNAL PATHWAY
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批准号:3468475
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项目类别:
-
资助金额:$9.83万
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财政年份:1991
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负责人:CHARLES S. HOFFMAN
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依托单位:
Characterization of the S. Pombe cAMP Pathway
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批准号:6732673
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项目类别:
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资助金额:$30.6万
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财政年份:1991
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负责人:CHARLES S. HOFFMAN
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依托单位:
S POMBE CAMP SIGNAL PATHWAY
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批准号:2183728
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项目类别:
-
资助金额:$11.13万
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财政年份:1991
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负责人:CHARLES S. HOFFMAN
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依托单位:
S POMBE CAMP SIGNAL PATHWAY
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批准号:2183731
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项目类别:
-
资助金额:$18.35万
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财政年份:1991
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负责人:CHARLES S. HOFFMAN
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依托单位:
CHARACTERIZATION OF THE S POMBE CAMP SIGNAL PATHWAY
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批准号:3468476
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项目类别:
-
资助金额:$10.42万
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财政年份:1991
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负责人:CHARLES S. HOFFMAN
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依托单位:
Characterization of the S. Pombe cAMP Pathway
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批准号:7020989
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项目类别:
-
资助金额:$10.3万
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财政年份:1991
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负责人:CHARLES S. HOFFMAN
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依托单位:
Characterization of the S. Pombe cAMP Pathway
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批准号:6519454
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项目类别:
-
资助金额:$30.43万
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财政年份:1991
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负责人:CHARLES S. HOFFMAN
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依托单位:
S POMBE CAMP SIGNAL PATHWAY
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批准号:2734701
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项目类别:
-
资助金额:$31.13万
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财政年份:1991
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负责人:CHARLES S. HOFFMAN
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依托单位:
S POMBE CAMP SIGNAL PATHWAY
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批准号:6018845
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项目类别:
-
资助金额:$32.23万
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财政年份:1991
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负责人:CHARLES S. HOFFMAN
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依托单位:
Characterization of the S. Pombe cAMP Pathway
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批准号:6326877
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项目类别:
-
资助金额:$30.6万
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财政年份:1991
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负责人:CHARLES S. HOFFMAN
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依托单位:
TRANSCRIPTIONAL REGULATION OF THE S POMBE FBPL GENE
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批准号:2468108
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项目类别:
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资助金额:$3.19万
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财政年份:1991
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负责人:CHARLES S. HOFFMAN
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依托单位:
Characterization of the S. Pombe cAMP Pathway
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批准号:6636033
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项目类别:
-
资助金额:$30.6万
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财政年份:1991
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负责人:CHARLES S. HOFFMAN
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依托单位:
S POMBE CAMP SIGNAL PATHWAY
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批准号:2183729
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项目类别:
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资助金额:$11.74万
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财政年份:1991
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负责人:CHARLES S. HOFFMAN
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依托单位:
海外基金