HGF family that includes HGF & HLP/MSP as a novel neurotrophic family

HGF 家族，包括 HGF

基本信息

批准号：
14580742
负责人：
FUNAKOSHI Hiroshi
金额：
$ 2.62万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

We previously indeitified that HGF and its family member, HGF-like protein (HLP)/MSP are novel neurotrophic factors for variety of neurons, such as cerebral cortex, hippocampus, midbrain dopaminergic, sensory, motor and sympathetic neurons. In the current study, we further investigated the roles of HGF and HLP in the nervous system, especially in neurodegenerative diseases. In addition, by generation and analyses of LIMK-2 KO mice, we found that LIM-kinase 2 play an important role in neuronal degenerative process.(1) Roles of HGF in amyotrophic lateral sclerosis (ALS): Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive loss of motoneurons and degeneration of motor axons. We showed that overexpression of hepatocyte growth factor (HGF) in the nervous system attenuates motoneuron death and axonal degeneration and prolongs the life span of transgenic mice overexpressing mutated SOD1. HGF prevented induction of caspase-1 in motoneurons an … More d retained the levels of the glial-specific glutamate transporter (EAAT2/GLT1) in reactive astrocytes. We propose that HGF may be the first example of an endogenous growth factor that can alleviate the symptoms of ALS by direct neurotrophic activities on motoneurons and indirect activities on glial cells, presumably favoring a reduction in glutamatergic neurotoxicity.(2) Roles of HLP/MSP in the nervous system: We previously reported that HLP act as a novel neurotrophic factor for chicken sensory neurons. Here we identified that Ron/HLP receptor is expressed in primary microglia and HLP accelerates microglial activities in vitro. Taken together with notion that HLP is neurotrophic, HLP may be one of the critical factor involving not only the protecting process of the neurodegeneration but also the degeneration and regeneration processes of the nervous system.(3) Roles of LIMKase-2 (LIMK2) in the nervous system: By generation and analyses if LIMK2 deficient mice, we found that limk2 variants were differently expressed in hippocampal neurons and play important roles in neurodegenerative process of hippocampal neurons. Less

我们先前概于HGF及其家人HGF样蛋白（HLP）/MSP是多种神经元的新型神经营养因素，例如大脑皮层，海马，中脑多巴胺能，感觉，感觉，运动和交感神经元。在当前的研究中，我们进一步研究了HGF和HLP在神经系统中的作用，尤其是在神经退行性疾病中。此外，通过对Limk-2 KO小鼠的生成和分析，我们发现Lim-激酶2在神经元退化过程中起着重要作用。（1）HGF在肌营养性侧索硬化症（ALS）中的作用：amyyotrophic hoplophic sclerosis（ALS）是致命的神经性疾病损失的致命性疾病损失，该疾病是渐进型序列的序言和渐进型序列的动力量及其动态的。我们表明，神经系统中肝细胞生长因子（HGF）的过表达减弱了运动神经元的死亡和轴突变性，并延长了过表达突变SOD1的转基因小鼠的寿命。 HGF阻止了运动神经元中caspase-1的诱导，并且更多的d保留了反应性星形胶质细胞中神经胶质特异性谷氨酸转运蛋白（EAAT2/GLT1）的水平。我们建议HGF可能是内源性生长因子的第一个例子，可以通过直接神经营养活性在运动神经元上和对神经胶质细胞的间接活性来减轻ALS的症状，这可能是有利于谷氨酸能神经毒性的降低。神经元。在这里，我们确定RON/HLP受体在原发性小胶质细胞中表达，HLP在体外加速了小胶质细胞活性。 Take together with notion that HLP is neurotrophic, HLP may be one of the critical factor involving not only the protecting process of the neurodegeneration but also the degeneration and regeneration processes of the nervous system.(3) Roles of LIMKase-2 (LIMK2) in the nervous system: By generation and analyses if LIMK2 deficient mice, we found that limk2 variants were differently expressed in hippocampal neurons and在海马神经元的神经退行性过程中起重要作用。较少的