Effects of nicotine on APP secretion and Aβ- or CT105-induced toxicity
Effects of nicotine on APP secretion and Aβ- or CT105-induced toxicity
复制标题
DOI：
10.1016/s0006-3223(00)01124-0
复制
发表时间：
2001-02-01
影响因子：
10.6
通讯作者：
Suh, YH
中科院分区：
文献类型：
--
作者：
Seo, JH;Kim, SH;Suh, YH
有证据表明淀粉样前体蛋白（APP）的过度表达或异常加工与阿尔茨海默病（AD）有因果关系。淀粉样前体蛋白主要在淀粉样β蛋白结构域内裂解以释放大的可溶性胞外域（APP），已知其具有广泛的营养功能。指导本综述的中心假设是尼古丁可能在APP分泌和APP代谢片段（β-淀粉样蛋白[A β]，羧基末端[CT]）诱导的毒性保护中发挥重要作用。我们的实验结果表明，尼古丁可促进APPs的释放，APPs具有神经营养和神经保护活性，且呈浓度依赖性（>50 μ mol/L）和时间依赖性（>2小时）。此外，尼古丁预处理（>10 μ mol/L，持续24小时）可部分阻止A β或CT 105诱导的原代培养神经元细胞毒性，尼古丁诱导的保护作用可被尼古丁α-银环蛇毒素预处理抑制。当用CT 105转染PC 12细胞时，尼古丁（>10 μ mol/L，持续24小时）部分抑制CT 105诱导的细胞毒性。从这些结果中，我们提出尼古丁或尼古丁受体激动剂治疗可能不仅通过补充胆碱能神经传递来改善认知功能，而且可能通过增加APPs的释放和激活尼古丁受体来保护A β或CT 105诱导的神经毒性。(C)2001生物精神病学学会。
Several lines of evidence indicated that overexpression or aberrant processing of amyloid precursor protein (APP) is causally related to Alzheimer's disease (AD). Amyloid precursor protein is principally cleaved within the amyloid beta protein domain to release a large soluble ectodomain (APPs), known to have a wide range of trophic functions. The central hypothesis guiding this review is that nicotine may play an important role in APP secretion and protection against toxicity induced by APP metabolic fragments (beta -amyloid [A beta], carboxyl terminal [CT]). Findings from our experiments have shown that nicotine enhances the release of APPs, which has neurotrophic and neuroprotective activities in concentration-dependent (>50 mu mol/L) and time-dependent (>2 hours) manners. In addition, pretreatment of nicotine (>10 mu mol/L for 24 hours) partially prevented A beta or CT105-induced cytotoxicity in primary cultured neuron cells, and the effects of nicotine-induced protection were inhibited by the pretreatment with a nicotine alpha -bungarotoxin. Nicotine (>10 mu mol/L for 24 hours) partially inhibited CT105-induced cytotoxicity when PC12 cells was transfected with CT105. From these results, we proposed that nicotine or nicotinic receptor agonist treatment might improve the cognitive functions not only by supplementation of cholinergic neurotransmission, but also by protecting A beta- or CT105-induced neurotoxicity probably through the increased release of APPs and the activation of nicotinic receptors. (C) 2001 Society of Biological Psychiatry.