Amyloid Beta Postsynaptic Signaling through AKAP-anchored Calcineurin

通过 AKAP 锚定的钙调神经磷酸酶进行淀粉样蛋白突触后信号传导

基本信息

批准号：
9180008
负责人：
MARK L DELL'ACQUA
金额：
$ 23.33万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9180008
关键词：
A kinase anchoring protein Adult Age Aging Alzheimer&apos s Disease Amyloid Amyloid beta-Protein Amyloid beta-Protein Precursor Brain Calcineurin Calcineurin inhibitor Calmodulin Cell Nucleus Chromosomes, Human, Pair 21 Chronic Conflict (Psychology)Cyclic AMP Cyclic AMP-Dependent Protein Kinases Data Dementia Dendritic Spines Development Diagnostic Docking Down Syndrome Drug Targeting Equilibrium Excision Excitatory Synapse Functional disorder Future Gene Expression General Population Genes Genetic Transcription Genetically Engineered Mouse Glutamate Receptor Hippocampus (Brain)Human Human Chromosomes Impaired cognition Individual Inherited Intellectual functioning disability Knock-in Mouse Laboratories Learning Light Link Long-Term Depression Long-Term Potentiation Mediating Memory Memory impairment Molecular Mus N-Methylaspartate Nerve Degeneration Neuronal Dysfunction Neuronal Plasticity Neurons Nuclear Translocation PPP3CA gene Pathology Pathway interactions Phenotype Phosphorylation Phosphotransferases Presenile Alzheimer Dementia Protein Dephosphorylation Protein Fragment Proteins Publishing Receptor Activation Regulation Reporting Research Rodent Rodent Model Role Scaffolding Protein Signal Pathway Signal Transduction Synapses Synaptic plasticity T cell regulation Testing Vertebral column abstracting calcineurin phosphatase cognitive function early onset innovation interest mouse model new therapeutic target novel novel diagnostics nuclear factors of activated T-cells overexpression postsynaptic prevent receptor response synaptic depression synaptic function targeted treatment tau Proteins transcription factor voltage

项目摘要

Project Summary Abstract Amyloid Beta Postsynaptic Signaling through AKAP-anchored Calcineurin A overproduction from APP is believed to contribute to impaired synaptic plasticity and decreased cognitive function in Alzheimer’s disease (AD). Individuals with Down syndrome (DS; trisomy 21) have an extra copy of APP that predisposes them to early-onset AD. Thus, elucidating how A inhibits plasticity is important for understanding cognitive impairments associated with the development of dementia in AD and DS and could identify novel drug targets, diagnostics, and therapies. Rodent model studies indicate that calcineurin (CaN) phosphatase signaling could contribute to altered LTP/LTD synaptic plasticity, dendritic spine loss, and learning and memory impairments in AD. A-induced spine loss may be further linked to altered gene expression through CaN activation of the transcription factor NFAT. Here we propose to test the novel hypotheses that AKAP79/150-CaN anchoring is required for A activation of CaN signaling that regulates the balance between LTP/LTD signaling and NFAT transcription associated with dendritic spine/synapse loss.

项目摘要摘要淀粉样蛋白β通过AKAP锚定钙化蛋白据信，App的过量生产会导致突触可塑性受损并精致阿尔茨海默氏病（AD）的认知功能。患有唐氏综合症的个体（DS;三体术21）有额外的使它们易于早发广告的应用程序的副本。阐明A抑制可塑性的重要性很重要了解与AD和DS中痴呆症发展相关的认知障碍，并且可以确定新型药物靶标，诊断和疗法。啮齿动物模型研究表明钙调神经酶（CAN）磷酸酶信号传导可能导致LTP/LTD合成可塑性，树突状丧失和 AD的学习和记忆力障碍。 A诱导的脊柱损失可能会进一步与基因改变有关通过转录因子NFAT激活的表达。在这里，我们建议测试小说假设AKAP79/150-CAN锚定是对调节的CAN信号的激活需要的 LTP/LTD信号传导与NFAT转录之间的平衡与树突状脊柱/突触损失相关。