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以甘油三酯形式补充二十二碳六烯酸(DHA)可预防多聚谷氨酰胺诱导的功能障碍。

Docosahexaenoic Acid (DHA) Supplementation in a Triglyceride Form Prevents from Polyglutamine-Induced Dysfunctions in .

作者信息

Mora Ignasi, Teixidó Alex, Vázquez-Manrique Rafael P, Puiggròs Francesc, Arola Lluís

机构信息

Brudy Technology S.L., 08006 Barcelona, Spain.

Universitat Rovira i Virgili, 43003 Tarragona, Spain.

出版信息

Int J Mol Sci. 2024 Nov 23;25(23):12594. doi: 10.3390/ijms252312594.

Abstract

A common hallmark of neurodegenerative diseases is the accumulation of polypeptide aggregates in neurons. Despite the primary cause of these diseases being inherently genetic, their development can be delayed with proper preventive treatments. Long-chain polyunsaturated fatty acids (ω-3 LCPUFA) are promising bioactive nutrients that are beneficial for brain health. In this study, the impact of an oil rich in a structured form of docosahexaenoic acid (DHA) triglyceride (TG) was assessed in a model expressing long poly-glutamine (polyQ) chains, which mimics the symptomatology of polyQ-related neurodegenerative diseases such as Huntington's disease (HD), among others. The lifespan, the motility, the number of polyQ aggregates, the oxidative stress resistance, and the cognitive performance associated with sensitive stimuli was measured in mutant nematodes with polyQ aggregates. Overall, DHA-TG at 0.5 µM improved the lifespan, the motility, the oxidative stress resistance, and the cognitive performance of the nematodes, emphasizing the protection against serotonergic synapse dysfunction. Furthermore, the treatment reduced the polyQ aggregates in the nematodes. The data described herein shed light on the connection between DHA and the cognitive performance in neurodegenerative diseases and demonstrated the potential of DHA-TG as nutritional co-adjuvant to prevent the development of polyQ-associated dysfunctions.

摘要

神经退行性疾病的一个常见特征是神经元中多肽聚集体的积累。尽管这些疾病的主要病因本质上是遗传性的,但通过适当的预防性治疗可以延缓其发展。长链多不饱和脂肪酸(ω-3 LCPUFA)是有前景的生物活性营养素,对大脑健康有益。在本研究中,在一个表达长聚谷氨酰胺(polyQ)链的模型中评估了富含结构化二十二碳六烯酸(DHA)甘油三酯(TG)的油的影响,该模型模拟了多聚谷氨酰胺相关神经退行性疾病如亨廷顿病(HD)等的症状。在具有多聚谷氨酰胺聚集体的突变线虫中测量了寿命、运动能力、多聚谷氨酰胺聚集体的数量、抗氧化应激能力以及与敏感刺激相关的认知表现。总体而言,0.5 µM的DHA-TG改善了线虫的寿命、运动能力、抗氧化应激能力和认知表现,强调了对血清素能突触功能障碍的保护作用。此外,该治疗减少了线虫中的多聚谷氨酰胺聚集体。本文所述的数据揭示了DHA与神经退行性疾病认知表现之间的联系,并证明了DHA-TG作为营养辅助剂预防多聚谷氨酰胺相关功能障碍发展的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11d9/11640917/7554944b5990/ijms-25-12594-g001.jpg

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