Nicotine promotes survival of cells expressing amyloid precursor protein and presenilin: implication for Alzheimer's disease.
Nicotine promotes survival of cells expressing amyloid precursor protein and presenilin: implication for Alzheimer's disease.
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尼古丁促进表达淀粉样蛋白前体蛋白质和寄生虫的细胞生存：对阿尔茨海默氏病的影响。
DOI：
10.1016/j.neulet.2012.12.046
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发表时间：
2013-02-22
影响因子：
2.5
通讯作者：
Tizabi Y
中科院分区：
文献类型：
--
作者：
Brown D;Ramlochansingh C;Manaye KF;Tizabi Y
淀粉样蛋白-β (a β)积累是阿尔茨海默病（AD）的主要标志之一，在其发病机制中起着至关重要的作用。淀粉样蛋白前体蛋白（APP）高度表达的细胞模型通常用于测试新型神经保护化合物的功效。除Aβ外，已知早老素蛋白突变有助于早发性AD。最近，一种同时表达APP和早老素的细胞性神经母细胞瘤模型已经出现。由于尼古丁对各种神经毒素的保护作用已经被观察到，本研究旨在确定尼古丁是否也能保护APP或APP和早老素引起的细胞损伤。用不同浓度的尼古丁预处理野生型神经母细胞瘤（N2a）细胞株和转染淀粉样蛋白前体蛋白（APP）、APP与早老素联合转染的神经母细胞瘤细胞株，采用MTT法测定细胞存活率。尼古丁剂量依赖性地对所有细胞系的细胞损失提供保护，双转染的保护最高（44%），其次是单转染（30%）和野生型（21%）。尼古丁的作用反过来被一种非选择性的尼古丁拮抗剂甲胺阻断。这些结果表明，代表阿尔茨海默病病理的细胞系对尼古丁的保护作用的不同敏感性，并进一步支持尼古丁激动剂对至少一种阿尔茨海默病亚型患者的治疗潜力。
Amyloid-β protein (Aβ) accumulation is one of the major hallmarks of Alzheimer’s disease (AD) and plays a crucial role in its pathogenesis. Cellular models whereby amyloid precursor protein (APP) is highly expressed are commonly used to test the efficacy of novel neuroprotective compounds. In addition to Aβ, it is known that mutation in the protein presenilin contributes to early onset AD. Recently, a cellular neuroblastoma model where both APP and presenilin are expressed has become available. Since protective effects of nicotine against various neurotoxins have been observed, this study was designed to determine whether nicotine would also protect against cellular damage induced by APP or APP and presenilin. Wild type neuroblastoma (N2a) cell line, and those transfected with amyloid precursor protein (APP), and the combination of APP and presenilin were pretreated with various concentrations of nicotine and the survivability of the cells were determined by MTT assay. Nicotine dose dependently provided protection against cellular loss in all cell lines, with highest protection in the double transfected (44%) followed by single transfected (30%), and wild type (21%). The effects of nicotine in turn were blocked by mecamylamine, a non-selective nicotinic antagonist. These results suggest differential sensitivity of cell lines representing AD pathology to the protective effects of nicotine and provide further support of therapeutic potential of nicotinic agonists in at least a subtype of AD patients.
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影响因子：
4.2
作者：
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通讯作者：
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