ROLE OF FGF IN NEURONAL INJURY

FGF 在神经元损伤中的作用

• 批准号: 6394521
• 负责人: FELIX P ECKENSTEIN
• 金额: $ 26.43万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-05 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6394521
• 关键词: cell cycle; fibroblast growth factor; genetically modified animals; growth factor receptors; laboratory mouse; motor neurons; nervous system regeneration; neural plasticity; receptor expression

DESCRIPTION (adapted from applicant's abstract): Acidic fibroblastic growth factor (FGF1) is a potent neurotrophic factor for most neuronal populations and a mitogen for many nonneuronal cell types. In the adult nervous system, specific neuronal populations express FGF1 in high levels, including motoneurons, basal forebrain cholinergic neurons and substantia nigra dopaminergic neurons. FGF1 lacks a hydrophobic signal peptide sequence, is not sorted to the secretory pathway, and may not be efficiently released from unstimulated healthy neurons. It is our hypothesis that injury causes the release of sufficient amounts of FGF1 to result in the activation of widely expressed transmembrane FGF receptors (FGFRs). This activation then provides autocrine neurotrophic support to damaged neurons and a paracrine activation signal to glial cells adjacent tot he damaged neurons. This hypothesis suggests that FGF1 is of great importance for the maintenance, plasticity and regeneration of motoneurons. Novel tools, including antibodies that specifically recognize the activated form of FGFRs and FGF1 knockout, FGF2 (a close relative of FGF1) knockout and FGF1/FGF2 double knockout mice will be used to test this hypothetical role of FGF1.

描述（改编自申请人的摘要）：酸性成纤维细胞生长 因子（FGF1）是大多数神经元种群和 许多非神经元细胞类型的有丝分裂原。在成人神经系统中， 特定的神经元种群以高水平表达FGF1，包括 运动神经元，基础前脑胆碱能神经元和黑质尼格拉 多巴胺能神经元。 FGF1缺乏疏水信号肽序列，不是 分类到分泌途径，可能不会有效地从 未刺激的健康神经元。我们的假设是伤害导致 释放足够数量的FGF1以导致广泛激活 表达的跨膜FGF受体（FGFR）。然后，此激活提供 对受损神经元和旁分泌激活的自分泌神经营养支持 向神经胶质细胞发出信号，邻近的神经元受损。该假设表明 FGF1对于维护，可塑性和 运动神经元的再生。新工具，包括抗体 特别识别FGFR和FGF1敲除的激活形式FGF2（A FGF1的亲戚）敲除和FGF1/FGF2双敲除小鼠将是 用于测试FGF1的假设作用。