申请人张杰博士，厦门大学教授，博导，主要从事老年痴呆症（AD）的细胞与分子致病机理研究。通过对神经元细胞周期调控与氧化应激长期系统地研究，申请人第一次发现和阐明了：1）AD致病过程中，细胞周期蛋白激酶CDK5在细胞核和细胞质分别行使了抑制细胞周期重新激活和神经元凋亡的双重功能。2）尼古丁对AD中氧化损伤的保护作用机制。至今发表论文23篇(第一或者通讯作者16篇)；回国独立开展工作以来，以通讯作者在PNAS，Journal of Neurosience，JBC，Clinical Cancer Research，Chemistry等杂志发表论文6篇；SCI他引358 次, H-index为13。本项目将着重研究AD致病过程中，细胞周期蛋白激酶的异常激活机理及其导致的神经功能紊乱的分子机制。这些研究结果对于阐明AD 的细胞与分子致病机制、发现AD 治疗靶标并开发新型治疗药物具有十分重要的意义。

The applicant candidate (Jie Zhang, Ph.D, Professor, Ph.D Supervisor in Xiamen University) focused on cellular and molecular pathogenesis mechanism of Alzheimer’s disease(AD).By the investigation on Neuronal cell cycle regulation and oxidative stress, Dr. Zhang firstly found and illustrated that Cycling Dependent Kinase 5 could inhibit the neuronal cell cycle reactivation in nucleus and attenuate neuronal death in cytoplasm during the pathogenesis of AD. The applicant has published 23 peered-reviewed research articles and invited reviews, among them 16 papers are published as first or corresponding author by the applicant, including 12 papers focused on CDK5 study (Two PNAS papers, Two Journal of Neuroscience papers, Two JBC papers et al). These publications were non-self cited almost 358 times, H-index is 13. The applicant has build an active research team after take the faculty position in Xiamen University, and will continue focus the research area on neuronal cell cycle regulation in AD. Our recent data found that the substrates of CDKs were dramatically phosphorylated in the neurons of AD, but little is known about the underlining mechanism and on neuronal functional consequence of these atypical activation of CDKs in AD. We will deep explore the molecular mechanism of neuronal dysfunction induced by atypical activation of CDKs, especially CDK3 and CDK5, try to find new AD-related CDK substrates, investigate the regulating mechanism of the activation of CDKs in AD. These works will benefit for understanding the cellular and molecular mechanism of the pathogenesis of AD, and also provide new prevention and curing target for pharmatheutical approach for AD.