Functional roles and mechanisms of ROS-dependent sumoylation in diabetic neuropathy (B06)

糖尿病神经病变(DPN)是一种常见的、使人衰弱且难以治疗的糖尿病晚期并发症。我们之前使用基因靶向小鼠的工作阐明了氧化应激相关轴突损伤和感觉异常的潜在机制，并表明外周感觉神经元和雪旺细胞中关键代谢蛋白和离子通道的总和作用在1型和2型糖尿病中都对糖尿病神经病变起到关键的保护作用。基于这些洞察力，在第三个资助期，我们现在的目标是阐明糖尿病先导如何阻碍和甲基化的保护功能，并制定巩固和甲基化的策略，以期阻止或逆转感觉丧失。

Diabetic neuropathy (DPN) is a frequent, debilitating and therapy-resistant late complication of diabetes. Our previous work using gene-targeted mice clarified mechanisms underlying oxidative stress-related axonal damage and sensory abnormalities and showed that sumoylation of key metabolic proteins and ion-channels in peripheral sensory neurons as well as Schwann cells plays a key protective role against diabetic neuropathy in both type 1 and type 2 diabetes. Based upon these insights, in the third funding period we now aim to elucidate how diabetes leads impedes the protective function of sumoylation and develop strategies to consolidate sumoylation with a view towards stopping or reversing sensory loss.