血小板活化因子在中枢神经系统中的双重活性及在新药开发中的价值

Dual activities of PAF in central nervous system and its values in development of new drugs

血小板活化因子(PAF)是一种产生于多种类型细胞的磷脂类物质,通过其特异性受体介导,诱发多种生物学效应。PAF在中枢神经系统生理和病理过程中发挥重要作用。在生理状态下,PAF作为一种逆向信使,通过调控突触信号传递及可塑性,提高突触长时程增强的效能,促进学习记忆,因此模拟PAF作用或调控PAF产生及灭活可望成为促智药开发的新目标。但在病理状态(如阿尔茨海默病、HIV相关性痴呆或脑缺血等)下,局部异常产生的PAF又可作为一种强效的炎症介质和神经毒素,加重中枢神经系统损伤。调控PAF的代谢及其效应(如阻断PAF受体)将成为干预阿尔茨海默病、HIV相关性痴呆以及脑缺血的重要策略。

Platelet-activating factor （PAF）, an endogenous bioactive lipid generated by phospholipase A2 and other pathways, displays a variety of biological activities in the nervous system. It has been suggested that PAF plays important roles in neuronal physiological functions including acting as a retrograde messenger to enhance synapse plasticity and memory formation, via activation of its specific membrane receptors. Therefore, the drugs that mimic the action of PAF or modulate the production and inactivation of PAF maybe promising in memory-enhancing. However, under certain pathological conditions, such as Alzheimer＇s disease, HIV-associated dementia or post-ischemic neuronal death, acting as a potent inflammatory mediator and neurotoxin, PAF has been implicated in the pathophysiology of brain injury. So, modulating the metabolism and effects of PAF （e. g., blocking the PAF receptor） may become important strategies of intervention of Alzheimer＇s disease, HIV-associated dementia or postischemic neuronal death.