阿尔茨海默病(Alzheimer’s disease, AD)是一种以认知障碍为主要特征的退行性神经疾病。神经元和突触损伤伴随神经递质功能异常,以及Aβ沉积和神经纤维缠结一直被认为是AD的主要标记。但由于病因复杂,目前针对该疾病仍无有效的治疗手段。本文将从中枢神经系统主要的神经递质及其受体方面对阿尔茨海默病治疗相关靶点进行综述。<br/>Alzheimer’s disease is neurodegenerative disease mainly characterized by cognitive impairment. Neuron and synapse loss together with neurotransmitter dysfunction have, along with Abdeposition and neurofibrillary tangles, been recognized as hallmarks of AD. However, there is still no a curative treatment for this devastating disease due to complexity of the pathophysiology of the disease. This article reviews relative treatment targets in Alzheimer’s disease from the aspects of main neurotransmitter and receptors in the central nervous system.
阿尔茨海默病,神经递质,G蛋白偶联受体, Alzheimer’s Disease Neurotransmitter G Protein-Coupled Receptors阿尔茨海默病治疗相关靶点研究进展
G. W. Arendash等发现对AD转基因(APPsw)小鼠进行长达6个月的A2AR拮抗剂咖啡因(0.3 g/L)摄入后,这些小鼠的认知损伤得到一定程度的改善,并且可溶性的Aβ水平恢复到了正常水平 [16] 。另外,一种核苷载体和腺苷受体的混合阻滞剂丙戊茶碱也被报道能减轻认知损伤,其机制可能与减少tau蛋白磷酸化有关 [17] 。
脑内血管紧张素(angiotensin, Ang)的AT4受体亚型在认知过程中作用的研究受到越来越多的重视,研究表明血管紧张素II (angiotensin II, Ang II)对记忆的增强作用可能是由于Ang II转化为Ang IV (angiotensin IV, Ang IV),而Ang IV作为AT4受体的激动剂发挥认知增强功能的 [23] 。在Ang IV类似物Nle1-Ang IV的基础上,John W. Wright和他的同事合成了一种代谢稳定、疏水性增强、能透过血脑屏障的口服小分子化合物N-hexanoic-Tyr-Ile-(6)amino hexanoic amide (Dihexa),并通过Morris水迷宫实验表明其能改善东莨菪碱引起的大鼠空间记忆能力障碍,预示着Dihexa或Dihexa类化合物可为AD治疗的药物设计提供一个新思路 [24] 。另外,据报道ACE抑制剂对轻度认知功能障碍患者具有稳定认知功能作用,且能减缓AD患者认知下降的速度 [25] 。
诸丽华,何 玲. 阿尔茨海默病治疗相关靶点研究进展 Research Progress for Relative Treatment Targets in Alzheimer’s Disease[J]. 药物资讯, 2016, 05(01): 1-7. http://dx.doi.org/10.12677/PI.2016.51001
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