Puangmalai Nicha, Thangnipon Wipawan, Soi-Ampornkul Rungtip, Suwanna Nirut, Tuchinda Patoomratana, Nobsathian Saksit
Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhonpathom, Thailand.
Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Neural Regen Res. 2017 Sep;12(9):1492-1498. doi: 10.4103/1673-5374.215262.
Alzheimer's disease, a progressive neurodegenerative disease, affects learning and memory resulting from cholinergic dysfunction. Scopolamine has been employed to induce Alzheimer's disease-like pathology and through alteration of cholinergic system. -benzylcinnamide (PT-3), purified from , has been shown to exhibit neuroprotective properties against amyloid-β-induced neuronal toxicity in rat cortical primary cell culture and to improve spatial learning and memory of aged rats through alleviating oxidative stress. We proposed a hypothesis that PT3 has a neuroprotective effect against scopolamine-induced cholinergic dysfunction. PT-3 (125-200 nM) pretreatment was performed in human neuroblastoma SH-SY5Y cell line following scopolamine induction. PT-3 (125-200 nM) inhibited scopolamine (2 mM)-induced generation of reactive oxygen species, cellular apoptosis, upregulation of acetylcholinesterase activity, downregulation of choline acetyltransferase level, and activation of p38 and JNK signalling pathways. These findings revealed the underlying mechanisms of scopolamine-induced Alzheimer's disease-like cellular dysfunctions, which provide evidence for developing drugs for the treatment of this debilitating disease.
阿尔茨海默病是一种进行性神经退行性疾病，由胆碱能功能障碍导致学习和记忆受损。东莨菪碱已被用于诱导阿尔茨海默病样病理，并通过改变胆碱能系统来实现。从[具体来源]中纯化得到的 -苄基肉桂酰胺（PT-3）已被证明在大鼠皮质原代细胞培养中对淀粉样蛋白β诱导的神经元毒性具有神经保护作用，并通过减轻氧化应激改善老年大鼠的空间学习和记忆。我们提出了一个假设，即PT3对东莨菪碱诱导的胆碱能功能障碍具有神经保护作用。在东莨菪碱诱导后，对人神经母细胞瘤SH-SY5Y细胞系进行PT-3（125 - 200 nM）预处理。PT-3（125 - 200 nM）抑制了东莨菪碱（2 mM）诱导的活性氧生成、细胞凋亡、乙酰胆碱酯酶活性上调、胆碱乙酰转移酶水平下调以及p38和JNK信号通路的激活。这些发现揭示了东莨菪碱诱导的阿尔茨海默病样细胞功能障碍的潜在机制，为开发治疗这种使人衰弱疾病的药物提供了证据。
