神经生长因子治疗阿尔采末病的胆碱能神经机制

神经生长因子 (nervegrowthfactor,NGF)是中枢胆碱能神经元存活和功能维持最重要的神经营养因子之一 ,对阿尔采末病 (Alzheimersdisease,AD)的治疗潜力已引起人们极大兴趣。投射于大脑皮质和海马的基底前脑胆碱能神经元退变是AD早期病变 ,也是导致患者认知功能降低的主要原因。NGF可通过兴奋残存神经元上高亲和性TrkA受体 ,促进中枢胆碱能神经元的存活和正常功能的发挥 ,同时神经元激活也使其自身免受AD的有害作用 ,即所谓“useitorloseit”现象。然而 ,NGF不能透过血脑屏障 ,如何使外源性NGF到达脑内靶区是亟待解决的难题 ,一旦获得理论和技术上的突破 ,NGF防治AD的临床应用才更具价值

Cholinergic basis of nerve growth factor in the treatment of Alzheimers disease

Nerve growth factor (NGF), one of the most potent growth factors for cholinergic neurons, has generated great interest as a potential target for the treatment of Alzheimers disease (AD). The degeneration of basal forebrain cholinergic neurons, which provides the major source of cholinergic innervation to the cerebral cortex and hippocampus, occurs early and contributes significantly to cognitive decline in AD. Those regions show high level expression of NGF and NGF receptors and depend on NGF for their survival and proper function. NGF executes its effects mainly by binding high affinity receptor TrkA in the remaining neurons of AD. Meanwhile, stimulation of neurons may protect those cells from the deleterious effects of AD, a phenomenon called “use it or lose it.”However, the use of NGF as therapeutic agent is limited by their hindered mobility through the blood brain barrier. Many theoretical and technical issues for NGF delivery to the target region in the brain remain to be solved, before NGF can live up to its potential for the treatment of AD.