ROLE OF FGF IN NEURONAL INJURY

描述(摘自申请者摘要)：酸性成纤维细胞生长 因子(FGF1)是一种强大的神经营养因子，对大多数神经元和 许多非神经细胞类型的有丝分裂原。在成人神经系统中， 特定的神经元群体高水平表达FGF1，包括 运动神经元、基底前脑胆碱能神经元和黑质 多巴胺能神经元。FGF1缺乏疏水信号肽序列，不是 排序到分泌途径，并且可能不能有效地从 未受刺激的健康神经元。我们的假设是损伤会导致 释放足够量的FGF1以导致广泛激活 表达跨膜成纤维细胞生长因子受体(FGFRs)。这种激活然后提供 对受损神经元的自分泌神经营养支持和旁分泌激活 向受损神经元附近的神经胶质细胞发出信号。这一假设表明 FGF1对细胞的维护、可塑性和 运动神经元的再生。新的工具，包括抗体 具体识别FGFRs和FGF1基因敲除的激活形式，FGF2(a FGF1)基因敲除和FGF1/FGF2双基因敲除小鼠的近亲将 用来测试FGF1的这一假设作用。

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.