神经元-突触丢失与老年痴呆

摘要/Abstract

摘要：阿尔茨海默病（AD）的基础和临床研究表明，老年斑和神经纤维缠结与痴呆程度无显著相关。在AD、血管性痴呆、额颞叶痴呆、路易体痴呆脑内均有明显突触丢失。神经元-突触丢失或突触丢失被认为是老年痴呆的主要原因。已发现Aβ和tau磷酸化过程中产生的寡聚体、突触外NMDA受体、含于突触后致密区的shank蛋白可导致突触丢失。因此，AD治疗的新方案包括:①用免疫治疗来清除Aβ寡聚体；②调节mTOR（一种使细胞存活的激酶）和UPS（泛素蛋白酶系统）活性，以维持突触蛋白的正常稳态平衡；③选择性激动突触NMDA受体或选择性拮抗突触外NMDA受体；④增加海马神经发生和增加突触新生。我们最近研究证明人参皂苷Rg1及其代谢产物Ppt能提高突触效能和结构可塑性，以及增加海马神经发生。提示该化合物有望成为防治神经元-突触丢失的药物。

关键词:神经元-突触丢失,老年痴呆,认知,突触长时程增强,NMDA受体,人参皂苷Rg1及Ppt,神经发生,突触新生

Abstract:Basic and clinical study of Alzheimer’s disease showed that senile plagues and neurofibrillary tangle are not related to the degree of cognitive impairment. Synaptic loss occur in Alzheimer’s disease and other neurodegenerative dementias which block LTP，induce neuropsychological dysfunction and memory deficit . Neuron-synapses or synaptic loss was considered as main cause of dementias. Several hidden toxins such as oligomer of Aβ and phosphorylated Tau,glutamate receptor at extrasynaptic region and shank protein can lead to synaptic loss. Therefore，strategy for AD treatment is that ① To clean oligomer by native oligomer of Aβ immunotherapy. ②To maintain the normal homeostasis of synaptic protein by mTOR(a protein kinase) and UPS. ③To activate synaptic NMDA receptors or block extrasynaptic NMDA receptors. ④To increase hippocampal neurogenesis and synaptogenesis. In our recent study，ginsenoside Rg1 and Ppt were proved to increase synaptic plasticity in both efficacy and structure as well as increase neurogenesis bothin vitroandin vivo，under physiological and pathological circumstances，indicating that they are promising agents for preventing and treatment of dementias and many kinds of memory impairment.

Key words:neuron-synapse loss,dementias,cognition,long-term ,potentiation(LTP),NMDA receptor,gensenoside Rg1 and Ppt,neurogenesis,synaptogenesis

张均田. 神经元-突触丢失与老年痴呆[J]. 神经药理学报, 2011, 1(1): 1-15.

ZHANG Juntian. Neuron-synapse loss and dementias[J]. Acta Neuropharmacologica, 2011, 1(1): 1-15.

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