SNRP at Hunter College

亨特学院 SNRP

• 批准号: 7349988
• 负责人: MITCHELL GOLDFARB
• 金额: $ 21.27万
• 依托单位: HUNTER COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349988
• 关键词: electrical potential; genes; neurons; physiology; proteins; sodium channel; syndrome; university

Fibroblast growth factor homologous factors (FHFs) are intracellular neuromodulators whose mechanisms of action are still poorly understood. Mice bearing deletions in Fhf genes display neurological deficits associated with motor function, although the animals show no detectable histological or immunohistochemical abnormalities. FHFs are believed to exert their effects through identified binding partners, which include voltage-gated sodium channels. Recent findings from the P.I.'s lab show that FHFs are required for proper intrinsic excitability of neurons, and that FHF-deficient neurons show aberrant voltage-dependent sodium channel behavior. Further data show that FHFs are required for optimal conduction of action potentials along motor axons. In light of these findings, this application proposes experiments to answer four related questions concerning FHF physiology: I. Do FHFs modulate neuronal excitability through direct FHF-sodium channel interactions? II. Are different FHF genes and protein isoforms equivalent or distinct in terms of sodium channel modulation and excitability? III. Does temporal regulation of FHF protein levels contribute to plasticity of intrinsic excitability? IV. Do FHF protein levels impact on the functional severity of demyelination syndromes? These experiments are expected to more fully define the mechanisms and conditions by which FHFs control physiology and pathophysiology of the central nervous system. More specifically, these studies will analyze FHF genes as potential contributors to severity of Charcot-Marie-Tooth syndrome and diabetic peripheral neuropathy, the latter of which constitutes a significant minority health disparity.

成纤维细胞生长因子同源因子（FHF）是细胞内的神经调质，其作用机制仍然知之甚少。携带Fhf基因缺失的小鼠显示与运动相关的神经功能缺损 功能，尽管动物没有显示出可检测的组织学或免疫组织化学异常。FHF是 据信，通过确定的结合伴侣发挥其作用，其中包括电压门控钠通道。 私家侦探的最新发现。的实验室表明，FHF是神经元固有兴奋性所必需的， FHF缺陷的神经元表现出异常的电压依赖性钠通道行为。进一步的数据显示，FHF是 这是动作电位沿着运动轴突最佳传导所需的。根据这些发现，本申请 提出实验来回答有关FHF生理学的四个相关问题： I. FHF是否通过与钠通道的直接相互作用来调节神经元的兴奋性？ 二.不同的FHF基因和蛋白质亚型在钠通道调节方面是相同的还是不同的， 兴奋性？ 三. FHF蛋白水平的时间调节是否有助于内在兴奋性的可塑性？ 四. FHF蛋白水平是否影响脱髓鞘综合征的功能严重程度？ 这些实验有望更全面地定义FHF控制生理学的机制和条件 和中枢神经系统的病理生理学。更具体地说，这些研究将分析FHF基因， Charcot-Marie-Tooth综合征和糖尿病周围神经病变严重程度的潜在因素，后者 这构成了一个重大的少数民族健康差距。