Pappolla M A, Sos M, Omar R A, Bick R J, Hickson-Bick D L, Reiter R J, Efthimiopoulos S, Robakis N K
Department of Pathology and Laboratory Medicine, University of South Alabama, Mobile, Alabama 36617, USA.
J Neurosci. 1997 Mar 1;17(5):1683-90. doi: 10.1523/JNEUROSCI.17-05-01683.1997.
Studies from several laboratories have generated evidence suggesting that oxidative stress is involved in the pathogenesis of Alzheimer's disease (AD). The finding that the amyloid beta protein (Abeta) has neurotoxic properties and that such effects are, in part, mediated by free radicals has provided insights into mechanisms of cell death in AD and an avenue to explore new therapeutic approaches. In this study we demonstrate that melatonin, a pineal hormone with recently established antioxidant properties, is remarkably effective in preventing death of cultured neuroblastoma cells as well as oxidative damage and intracellular Ca2+ increases induced by a cytotoxic fragment of Abeta. The effects of melatonin were extremely reproducible and corroborated by multiple quantitative methods, including cell viability studies by confocal laser microscopy, electron microscopy, and measurements of intracellular calcium levels. The importance of this finding is that, in contrast to conventional antioxidants, melatonin has a proposed physiological role in the aging process. Secretion levels of this hormone are decreased in aging and more severely reduced in AD. The reported phenomenon may be of therapeutic relevance in AD.
多个实验室的研究已产生证据表明氧化应激参与了阿尔茨海默病（AD）的发病机制。淀粉样β蛋白（Aβ）具有神经毒性特性，且这种效应部分由自由基介导，这一发现为AD中的细胞死亡机制提供了见解，并为探索新的治疗方法开辟了道路。在本研究中，我们证明褪黑素是一种最近被证实具有抗氧化特性的松果体激素，在预防培养的神经母细胞瘤细胞死亡以及由Aβ细胞毒性片段诱导的氧化损伤和细胞内Ca2+增加方面非常有效。褪黑素的作用极具重复性，并通过多种定量方法得到证实，包括共聚焦激光显微镜、电子显微镜进行的细胞活力研究以及细胞内钙水平的测量。这一发现的重要性在于，与传统抗氧化剂不同，褪黑素在衰老过程中具有假定的生理作用。这种激素的分泌水平在衰老过程中会降低，而在AD中会更严重地降低。所报道的现象可能与AD的治疗相关。
