Institute of Biotechnology, Federal University of Uberlândia, Uberlândia, MG, Brazil.
Laboratory of Genetics, Institute of Biotechnology, Federal University of Uberlândia, Acre Street, 2E building, room 230, Uberlândia, MG, 38405-319, Brazil.
Sci Rep. 2022 Jun 30;12(1):11065. doi: 10.1038/s41598-022-15297-1.
Alzheimer's disease (AD) is the most common form of dementia in the elderly, affecting cognitive, intellectual, and motor functions. Different hypotheses explain AD's mechanism, such as the amyloidogenic hypothesis. Moreover, this disease is multifactorial, and several studies have shown that gut dysbiosis and oxidative stress influence its pathogenesis. Knowing that kefir is a probiotic used in therapies to restore dysbiosis and that the bioactive peptides present in it have antioxidant properties, we explored its biotechnological potential as a source of molecules capable of modulating the amyloidogenic pathway and reducing oxidative stress, contributing to the treatment of AD. For that, we used Drosophila melanogaster model for AD (AD-like flies). Identification of bioactive peptides in the kefir sample was made by proteomic and peptidomic analyses, followed by in vitro evaluation of antioxidant and acetylcholinesterase inhibition potential. Flies were treated and their motor performance, brain morphology, and oxidative stress evaluated. Finally, we performed molecular docking between the peptides found and the main pathology-related proteins in the flies. The results showed that the fraction with the higher peptide concentration was positive for the parameters evaluated. In conclusion, these results revealed these kefir peptide-rich fractions have therapeutic potential for AD.
阿尔茨海默病（AD）是老年人中最常见的痴呆症形式，影响认知、智力和运动功能。不同的假说解释了 AD 的发病机制，如淀粉样蛋白假说。此外，这种疾病是多因素的，几项研究表明，肠道菌群失调和氧化应激会影响其发病机制。由于知道开菲尔是一种用于恢复菌群失调的益生菌，并且其中存在的生物活性肽具有抗氧化特性，我们探索了其生物技术潜力，作为一种能够调节淀粉样蛋白途径和降低氧化应激的分子来源，从而有助于 AD 的治疗。为此，我们使用了用于 AD 的黑腹果蝇模型（AD 样果蝇）。通过蛋白质组学和肽组学分析对开菲尔样品中的生物活性肽进行了鉴定，然后对其抗氧化和乙酰胆碱酯酶抑制潜力进行了体外评估。对苍蝇进行了处理，并评估了它们的运动性能、大脑形态和氧化应激。最后，我们对发现的肽与苍蝇中与主要病理相关的蛋白质之间进行了分子对接。结果表明，肽浓度较高的部分对评估的参数呈阳性。总之，这些结果表明这些富含开菲尔肽的部分具有治疗 AD 的潜力。
