The role of Anaplastic Lymphoma Kinase in motor neuron survival

描述（由申请人提供）：临床和基础神经科学的一个主要目标是确定可以促进脊髓运动神经元存活的因素。尽管已经鉴定出几种可以支持运动神经元的神经营养因子，但我们仍然无法在体内拯救大多数运动神经元。该提案的目的是确定一种相对新颖的受体酪氨酸激酶，间变性淋巴瘤激酶（ALK）在脊髓运动神经元中的功能。基于我们的初步数据，包括ALK在程序性细胞死亡（PCD）期间在脊髓运动神经元中动态表达的事实，我们假设ALK促进脊髓运动神经元的存活。我们将通过对卵内ALK表达鸡胚进行功能获得和丧失操作来检验这一假设，并确定对脊髓运动神经元存活的影响。公共卫生相关性：如果脊髓运动神经元死亡，就会导致瘫痪。运动神经元在发育障碍如脊髓性肌萎缩症和成人发病的障碍如肌萎缩性侧索硬化症（卢伽雷氏病）和脊髓损伤后死亡。我们已经确定了一种蛋白质，间变性淋巴瘤激酶，这是表达在脊髓运动神经元。我们的初步数据表明，降低这种蛋白质的水平会导致脊髓运动神经元的死亡。这项研究的目的是增加这种蛋白质的水平，以测试我们是否可以拯救垂死的脊髓运动神经元。这项工作可能会导致新的治疗方法，促进运动神经元在神经疾病中的生存。

DESCRIPTION (provided by applicant): A major goal in clinical and basic neuroscience is to identify factors that can promote the survival of spinal motor neurons. Despite the identification of several neurotrophic factors that can support motor neurons, we are still incapable of rescuing the majority of motor neurons in vivo. The goal of this proposal is to determine the function of a relatively novel receptor tyrosine kinase, Anaplastic Lymphoma Kinase (ALK), in spinal motor neurons. Based on our preliminary data including the fact ALK is dynamically expressed in spinal motor neurons during the period of programmed cell death (PCD), we hypothesize that ALK promotes the survival of spinal motor neurons. We will test this hypothesis by conducting gain and loss-of-function manipulations of ALK expression chick embryos in ovo and determine the effects on spinal motor neuron survival. PUBLIC HEALTH RELEVANCE: If spinal motor neurons die, paralysis results. Motor neurons die in developmental disorders such as Spinal Muscular Atrophy and in adult-onset disorders such as Amyotrophic Lateral Sclerosis (Lou Gehrig's disease) and following spinal cord injury. We have identified a protein, Anaplastic lymphoma kinase, which is expressed on spinal motor neurons. Our preliminary data indicates that reducing levels of this protein causes the death of spinal motor neurons. The goal of this study is to increase levels of this protein to test whether we can rescue dying spinal motor neurons. This work could lead to novel therapeutics for promoting the survival of motor neurons in neural disease.