创伤性脑损伤（TBI）发生率高、致残率高，是导致青壮年死亡的主要原因。虽然针对TBI开展了大量的基础和临床研究，但TBI后的分子病理机制尚未完全阐明，并缺乏有效的临床药物干预措施。申请人的前期研究表明，突触后致密物质（PSD）中的代谢型谷氨酸受体（mGluR）和突触后支架蛋白Homer形成复合体，在TBI调控过程中发挥关键作用。本课题拟利用已建立的TBI研究平台，明确mGluR-Homer复合体磷酸化在TBI中的作用，阐明突触后支架蛋白Preso调控mGluR-Homer复合体磷酸化的机制，并探索Preso调节mGluR-Homer复合体磷酸化在TBI病理过程中的生物学效应。本课题以mGluR-Homer复合体磷酸化为切入点，将Preso作为核心分子，在体内外研究TBI的调控机制，有望进一步建立TBI后PSD分子调控网络，为TBI治疗提供新靶点和新策略。

Traumatic brain injury (TBI) has high incidence and morbidity, which is a major cause of death in young people. Although there are a lot of laboratory and clinical investigations on TBI, molecular mechanism underlying TBI is still unclear and drug treatment in clinical practice is limited. Previous studies of proposer indicated that complex formed by metabotropic glutamate receptor (mGluR) and postsynaptic scaffold protein Homer in postsynaptic density (PSD) played crucial roles in regulation of TBI. On the basis of established research platform for TBI, proposer plan to clarify the role of mGluR-Homer complex phosphorylation in TBI, elucidate molecular mechanism underlying postsynaptic scaffold protein Preso in regulating phosphorylation of mGluR-Homer complex, and investigate the biological effects of Preso-mediated mGluR-Homer complex phosphorylation in pathological process of TBI. This project focus on Preso and its regulatory effects on phosphorylation of mGluR-Homer complex in TBI. It is expected to further establish the PSD signaling network following TBI, and provide novel drug targets and treatment strategies for TBI.