Role of JNK in Neuronal Apoptosis

描述(由申请人提供)：本申请的目标是 确定糖尿病后根神经病变的分子机制 神经节(DRG)神经元。我们的假设是暴露在高糖环境下的神经元 通过激活凋亡信号调节蛋白1(Aski)进行细胞凋亡， 激活c-jun氨基末端激酶(JNK)途径。胰岛素样生长 胰岛素样生长因子I(IGF-I)被预测通过以下途径保护DRG免受葡萄糖介导的细胞凋亡 阻断JNK途径的一个组成部分的激活。此应用程序将 用原位末端标记法和免疫印迹法检测葡萄糖处理后的背根节 1)JNK激活诱导的细胞凋亡分子；2)Aski在JNK中的作用 3)IGF-I对JNK通路激活的影响 和细胞凋亡调节蛋白。在这些研究结束后，我们将 了解JNK通路在糖尿病神经病变模型中的作用 IGF-I如何调节神经保护。这些发现将推动我们的 对神经元损伤的了解，并可能建议潜在的治疗方法 治疗糖尿病神经病变的干预措施。

DESCRIPTION (provided by applicant): The goal of this application is to determine the molecular mechanism underlying diabetic neuropathy in dorsal root ganglion (DRG) neurons. Our hypothesis is that neurons exposed to high glucose undergo apoptosis via activation of apoptosis signal-regulated kinase 1 (ASKI), which activates the c-Jun N-terminal kinase (JNK) pathway. Insulin-like growth factor I (IGF-I) is predicted to protect DRG from glucose-mediated apoptosis by blocking activation of a component of the JNK pathway. This application will analyze glucose-treated DRG by TUNEL analysis and western blotting to determine 1) apoptotic molecules induced by JNK activation, 2) the role of ASKI on JNK activation and apoptosis and 3) the effect of IGF-I on JNK pathway activation and apoptotic regulatory proteins. At the conclusion of these studies we will understand how the JNK pathway functions in a model of diabetic neuropathy and how IGF-I mediates neuroprotection. These findings will advance our understanding of neuronal injury and may suggest potential therapeutic interventions for treatment of diabetic neuropathy.