Mechanisms of Neurodegeneration

描述（由申请人提供）：本研究计划的总体目标是了解哺乳动物细胞中MAP激酶介导的信号转导机制。本研究的重点是MAP激酶的c-Jun NH 2-末端激酶（JNK）组。JNK蛋白激酶级联的许多组分已通过分子克隆鉴定，并已在生化研究中表征。然而，JNK的生理功能的完整理解仍然是难以捉摸的。本研究的长期目标是明确JNK激活的分子机制和生理意义。我们分析的一个具体重点将是确定JNK在神经退行性变中的作用。 本研究目标的实现将有助于进一步了解MAP激酶在体内信号转导的分子机制。这些信息为设计治疗神经退行性疾病（包括中风）的新治疗策略奠定了基础。 该提案的具体目标是审查： 1. JNK在神经元中的生理作用。 2. JNK诱导神经元变性的机制。

DESCRIPTION (provided by applicant): The overall goal of this research program is to understand the mechanism of signal transduction mediated by MAP kinases in mammalian cells. A focus of this study is the c-Jun NH2-terminal kinase (JNK) group of MAP kinases. Many of the components of the JNK protein kinase cascade have been identified by molecular cloning and have been characterized in biochemical studies. However, a complete understanding of the physiological function of JNK has remained elusive. The long-term goal of this research is to define the molecular mechanisms and physiological significance of JNK activation in neurons. A specific focus of our analysis will be to determine the role of JNK in neurodegeneration. Achievement of the goals of this proposal will increase understanding of the molecular mechanism of MAP kinase signal transduction in vivo. This information represents a basis for the design of novel therapeutic strategies for the treatment of neurodegenerative diseases, including stroke. The Specific Aims of this proposal are to examine: 1. The physiological role of JNK in neurons. 2. The mechanism of JNK-induced neurodegeneration.