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天然产物姜黄素作为阿尔茨海默病治疗中的潜在辅助药物。

The Natural Product Curcumin as a Potential Coadjuvant in Alzheimer's Treatment.

作者信息

Morales Inelia, Cerda-Troncoso Cristóbal, Andrade Víctor, Maccioni Ricardo B

机构信息

Laboratory of Cellular and Molecular Neurosciences, Faculty of Sciences, University of Chile, Santiago, Chile.

International Center for Biomedicine (ICC), Santiago, Chile.

出版信息

J Alzheimers Dis. 2017;60(2):451-460. doi: 10.3233/JAD-170354.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive cognitive impairment of patients, affecting around 12% of people older than 65 years old. WHO estimated that over 48.6 million all over the world suffer this disease. On the basis of cumulative results on our research, we have postulated the neuroimmunomodulation hypothesis that appears to provide a reasonable explanation of both the preclinical and clinical observations. In this context, the long-term activation of the innate immune system triggers an anomalous cascade of molecular signals, finally leading to tau oligomerization in the pathway to neuronal degeneration. In the present scenario of the failure of many anti-AD drugs, nutraceutical compounds provide an avenue for AD prevention and possibly as coadjuvants in the treatment of this disease. Recent discoveries point to the relevance of curcumin, a natural anti-inflammatory agent, in controlling oxidative stress and improving cholinergic function in the brain, even though the mechanisms underlying these actions are unknown. We investigated the effects of curcumin in cultures of neuronal cells. For this study, we exposed cells to prooxidant conditions, both in the presence and absence of curcumin. Our data reveal that curcumin exert a strong neuroprotective effect in N2a cells, thus preventing toxicity by oxidative agents H2O2 and Fe+3. This is supported by results that indicate that curcumin control the neurodegenerative effects of both oxidative agents, relieving cells from the loss of neuritogenic processes induced by prooxidants. In addition, curcumin was able to slow down the tau aggregation curve and disassemble tau pathological oligomeric structures. Data suggest that curcumin could be a potential compound for prevention of cognitive disorders associated with AD.

摘要

阿尔茨海默病(AD)是一种神经退行性疾病,其特征是患者出现进行性认知障碍,影响约12%的65岁以上人群。世界卫生组织估计,全球超过4860万人患有这种疾病。基于我们研究的累积结果,我们提出了神经免疫调节假说,该假说似乎为临床前和临床观察结果提供了合理的解释。在这种情况下,先天免疫系统的长期激活会引发异常的分子信号级联反应,最终导致神经元变性途径中的tau蛋白寡聚化。在目前许多抗AD药物失效的情况下,营养化合物为AD的预防提供了一条途径,并且可能作为这种疾病治疗的辅助剂。最近的发现指出了天然抗炎剂姜黄素在控制氧化应激和改善大脑胆碱能功能方面的相关性,尽管这些作用的潜在机制尚不清楚。我们研究了姜黄素在神经元细胞培养中的作用。在本研究中,我们将细胞置于有或没有姜黄素的促氧化条件下。我们的数据显示,姜黄素在N2a细胞中发挥强大的神经保护作用,从而预防氧化试剂H2O2和Fe+3的毒性。这一结果得到了以下结果的支持:这些结果表明,姜黄素可控制两种氧化试剂的神经退行性作用,使细胞免受促氧化剂诱导的神经突生成过程丧失的影响。此外,姜黄素能够减缓tau蛋白聚集曲线并拆解tau蛋白病理性寡聚结构。数据表明,姜黄素可能是预防与AD相关的认知障碍的潜在化合物。

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