Alzheimer's disease: Targeting the Cholinergic System.
Alzheimer's disease: Targeting the Cholinergic System.
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DOI：
10.2174/1570159x13666150716165726
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发表时间：
2016
影响因子：
5.3
通讯作者：
Ribeiro FM
中科院分区：
文献类型：
--
作者：
Ferreira-Vieira TH;Guimaraes IM;Silva FR;Ribeiro FM
乙酰胆碱（Acetylcholine，ACh）在外周和中枢神经系统中具有重要作用。胆碱乙酰转移酶（ChAT）负责在细胞质中从乙酰辅酶A和胆碱合成ACh，囊泡乙酰胆碱转运体（VAChT）将神经递质摄取到突触囊泡中。去极化后，ACh经历胞吐作用到达突触间隙，在那里它可以结合其受体，包括毒蕈碱受体和尼古丁受体。存在于突触间隙的ACh被乙酰胆碱酯酶（AChE）迅速水解，形成乙酸盐和胆碱，其通过高亲和力胆碱转运蛋白（CHT1）再循环到突触前神经末梢。位于基底前脑的胆碱能神经元，包括形成Meynert基底核的神经元，在阿尔茨海默病（AD）中严重丢失。AD是痴呆症的最常见原因，影响全球2500万人。这种疾病的特征是神经纤维缠结和淀粉样斑块的积累。然而，皮质斑块的水平与AD相关的认知障碍之间没有真实的相关性。然而，突触丧失是疾病进展的主要相关因素，胆碱能神经元的丧失导致记忆和注意力缺陷。因此，作用于胆碱能系统的药物代表了治疗AD患者的有希望的选择。
Acetylcholine (ACh) has a crucial role in the peripheral and central nervous systems. The enzyme choline acetyltransferase (ChAT) is responsible for synthesizing ACh from acetyl-CoA and choline in the cytoplasm and the vesicular acetylcholine transporter (VAChT) uptakes the neurotransmitter into synaptic vesicles. Following depolarization, ACh undergoes exocytosis reaching the synaptic cleft, where it can bind its receptors, including muscarinic and nicotinic receptors. ACh present at the synaptic cleft is promptly hydrolyzed by the enzyme acetylcholinesterase (AChE), forming acetate and choline, which is recycled into the presynaptic nerve terminal by the high-affinity choline transporter (CHT1). Cholinergic neurons located in the basal forebrain, including the neurons that form the nucleus basalis of Meynert, are severely lost in Alzheimer’s disease (AD). AD is the most ordinary cause of dementia affecting 25 million people worldwide. The hallmarks of the disease are the accumulation of neurofibrillary tangles and amyloid plaques. However, there is no real correlation between levels of cortical plaques and AD-related cognitive impairment. Nevertheless, synaptic loss is the principal correlate of disease progression and loss of cholinergic neurons contributes to memory and attention deficits. Thus, drugs that act on the cholinergic system represent a promising option to treat AD patients.