ROLE OF FGF IN NEURONAL INJURY

描述（改编自申请人摘要）：酸性成纤维细胞生长 因子（FGF 1）是大多数神经元群体的有效神经营养因子， 许多非神经细胞类型的促分裂原。在成人的神经系统中， 特定的神经元群体以高水平表达FGF 1，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FGF 1缺乏疏水信号肽序列， 被分类到分泌途径，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， 释放足够量的FGF 1，导致广泛的 表达的跨膜FGF受体（FGFR）。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， FGF 1对维持、可塑性和 运动神经元的再生。新的工具，包括抗体， 特异性识别激活形式的FGFR和FGF 1敲除，FGF 2（a FGF 1）敲除和FGF 1/FGF 2双敲除小鼠的近亲 用于测试FGF 1的假设作用。

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.