Belkacemi Abdenour, Ramassamy Charles
INRS- Institut Armand Frappier, 531, boul. des Prairies, Laval, Quebec, H7V 1B7, Canada.
Cent Nerv Syst Agents Med Chem. 2015;16(1):37-49. doi: 10.2174/1871524915666150730125532.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder of aging. It is a multifactorial disease with several overlapping pathways. Therefore, successful therapy should target several pathological features simultaneously. In this regard, cumulative data have demonstrated that polyphenols can display neuroprotective effects through different mechanisms. In this study, we tested the hypothesis that a mixture of anthocyanins/anthocyanidins presents in the formulation MAF14001 may mitigate the amyloid-β peptide (Aβ) toxicity. Anthocyanins are a class of polyphenols capable to cross the blood brain barrier and their intake is associated to a reduced risk of some several chronic diseases. Our results showed that the formulation MAF14001 can protect SK-N-SH cells against Aβ-induced toxicity. From 5 µM, MAF14001 protected SK-N-SH cells against Aβ toxicity by preventing oxidative stress, mitochondrial dysfunction and apoptosis. Furthermore, MAF14001 might directly interact with Aβ to prevent its aggregation process, a key process on Aβ-induced oxidative stress. Indeed, in the presence of MAF14001, Aβ was less susceptible to fibrillation. Finally, MAF14001 decreased the tau phosphorylation (Ser-202) induced by Aβ. Altogether, these results demonstrated that MAF14001 could target multiple mechanisms involved in the etiology of AD and could be useful in preventing and treating AD.
阿尔茨海默病(AD)是衰老过程中最常见的神经退行性疾病。它是一种具有多种重叠途径的多因素疾病。因此,成功的治疗应同时针对多种病理特征。在这方面,累积数据表明多酚可以通过不同机制发挥神经保护作用。在本研究中,我们检验了以下假设:MAF14001制剂中存在的花青素/花色素苷混合物可能减轻淀粉样β肽(Aβ)的毒性。花青素是一类能够穿过血脑屏障的多酚,其摄入与多种慢性疾病风险降低有关。我们的结果表明,MAF14001制剂可以保护SK-N-SH细胞免受Aβ诱导的毒性。从5μM起,MAF14001通过预防氧化应激、线粒体功能障碍和细胞凋亡来保护SK-N-SH细胞免受Aβ毒性。此外,MAF14001可能直接与Aβ相互作用以阻止其聚集过程,这是Aβ诱导氧化应激的关键过程。事实上,在MAF14001存在的情况下,Aβ不易发生纤维化。最后,MAF14001降低了Aβ诱导的tau蛋白磷酸化(Ser-202)。总之,这些结果表明MAF14001可以针对AD病因学中涉及的多种机制,可能对预防和治疗AD有用。