Ding Xiling, MacTavish David, Kar Satyabrata, Jhamandas Jack H
Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Neurobiol Dis. 2006 Feb;21(2):413-20. doi: 10.1016/j.nbd.2005.08.016. Epub 2005 Oct 24.
In brains of Alzheimer's disease (AD) patients, expression of the neuropeptide galanin is significantly upregulated and galanin-immunoreactive fibers hypertrophy and hyperinnervate cholinergic neurons of the basal forebrain. However, the role of galanin in AD, whether it is detrimental or neuroprotective, remains controversial. In this study, using primary cultured neurons from the rat basal forebrain, we show that pretreatment with galanin protects cholinergic neurons against beta-amyloid-induced apoptotic cell death as judged by visual observation, MTT assay, Live/dead cell assay, TUNEL and cleaved caspase-3 staining. These effects are mimicked by the galanin receptor 2 (GALR2) agonist, AR-M1896. Western blot analysis revealed Abeta-induced decrease in phospho-PKC and phospho-Akt levels was reversed by galanin. Galanin also attenuated cleavage of caspases-3 and -9 following exposure to Abeta. These findings support a neuroprotective role for galanin and may have implications for development of compounds based on this peptide to treat AD.
在阿尔茨海默病（AD）患者的大脑中，神经肽甘丙肽的表达显著上调，且甘丙肽免疫反应性纤维肥大，并过度支配基底前脑的胆碱能神经元。然而，甘丙肽在AD中的作用，无论是有害的还是具有神经保护作用，仍然存在争议。在本研究中，我们使用大鼠基底前脑的原代培养神经元，通过视觉观察、MTT法、活/死细胞检测、TUNEL和裂解的半胱天冬酶-3染色判断，结果表明用甘丙肽预处理可保护胆碱能神经元免受β-淀粉样蛋白诱导的凋亡性细胞死亡。甘丙肽受体2（GALR2）激动剂AR-M1896可模拟这些作用。蛋白质印迹分析显示，甘丙肽可逆转β-淀粉样蛋白诱导的磷酸化蛋白激酶C（PKC）和磷酸化蛋白激酶B（Akt）水平降低。暴露于β-淀粉样蛋白后，甘丙肽还可减弱半胱天冬酶-3和-9的裂解。这些发现支持了甘丙肽具有神经保护作用，并且可能对基于该肽开发治疗AD的化合物具有启示意义。
