Role of JNK in Neuronal Apoptosis

描述（由申请人提供）：本申请的目标是 确定糖尿病背根神经病变的分子机制 神经节（DRG）神经元。我们的假设是暴露于高葡萄糖的神经元 通过激活凋亡信号调节激酶1（ASKI）进行凋亡， 其激活c-Jun N-末端激酶（JNK）途径。胰岛素样生长 I因子（IGF-I）被预测通过以下途径保护DRG免受葡萄糖介导的凋亡： 阻断JNK途径的一个组分的激活。此应用程序将 通过TUNEL分析和蛋白质印迹分析葡萄糖处理的DRG，以确定 1)JNK激活诱导的凋亡分子; 2）ASKI对JNK的作用 3）IGF-I对JNK通路活化的影响 和凋亡调节蛋白。在这些研究结束时，我们将 了解JNK通路如何在糖尿病神经病变模型中发挥作用， IGF-I如何介导神经保护作用。这些发现将推动我们 了解神经元损伤，并可能建议潜在的治疗 治疗糖尿病神经病变的干预。

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.