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生物因素联合作用对阿尔茨海默病模型生物能量学参数、Aβ 水平和存活的影响。

Effects of Combining Biofactors on Bioenergetic Parameters, Aβ Levels and Survival in Alzheimer Model Organisms.

机构信息

Biomedical Research Center Seltersberg (BFS), Laboratory for Nutrition in Prevention and Therapy, Institute of Nutritional Sciences, Justus Liebig University Giessen, Schubertstr. 81, 35392 Giessen, Germany.

出版信息

Int J Mol Sci. 2022 Aug 4;23(15):8670. doi: 10.3390/ijms23158670.

DOI:10.3390/ijms23158670
PMID:35955803
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9368976/
Abstract

Increased amyloid beta (Aβ) levels and mitochondrial dysfunction (MD) in the human brain characterize Alzheimer disease (AD). Folic acid, magnesium and vitamin B6 are essential micro-nutrients that may provide neuroprotection. Bioenergetic parameters and amyloid precursor protein (APP) processing products were investigated in vitro in human neuroblastoma SH-SY5Y-APP695 cells, expressing neuronal APP, and in vivo, in the invertebrate (CL2006 & GMC101) expressing muscular APP. Model organisms were incubated with either folic acid and magnesium-orotate (ID63) or folic acid, magnesium-orotate and vitamin B6 (ID64) in different concentrations. ID63 and ID64 reduced Aβ, soluble alpha APP (sAPPα), and lactate levels in SH-SY5Y-APP695 cells. The latter might be explained by enhanced expression of lactate dehydrogenase (LDHA). Micronutrient combinations had no effects on mitochondrial parameters in SH-SY5Y-APP695 cells. ID64 showed a significant life-prolonging effect in CL2006. Incubation of GMC101 with ID63 significantly lowered Aβ aggregation. Both combinations significantly reduced paralysis and thus improved the phenotype in GMC101. Thus, the combinations of the tested biofactors are effective in pre-clinical models of AD by interfering with Aβ related pathways and glycolysis.

摘要

人脑中淀粉样蛋白β (Aβ) 水平升高和线粒体功能障碍 (MD) 是阿尔茨海默病 (AD) 的特征。叶酸、镁和维生素 B6 是必需的微量营养素，可能提供神经保护。在体外研究了表达神经元 APP 的人神经母细胞瘤 SH-SY5Y-APP695 细胞中的生物能量学参数和淀粉样前体蛋白 (APP) 加工产物，以及在表达肌 APP 的无脊椎动物 (CL2006 和 GMC101) 中体内的情况。用叶酸和镁-5-核苷酸 (ID63) 或叶酸、镁-5-核苷酸和维生素 B6 (ID64) 以不同浓度孵育模型生物。ID63 和 ID64 降低了 SH-SY5Y-APP695 细胞中的 Aβ、可溶性 alpha APP (sAPPα) 和乳酸水平。后者可能是通过增强乳酸脱氢酶 (LDHA) 的表达来解释的。微量营养素组合对 SH-SY5Y-APP695 细胞中的线粒体参数没有影响。ID64 在 CL2006 中表现出显著的延长寿命作用。用 ID63 孵育 GMC101 可显著降低 Aβ 聚集。两种组合均显著降低了 GMC101 的瘫痪，从而改善了表型。因此，所测试的生物因子组合通过干扰与 Aβ 相关的途径和糖酵解，在 AD 的临床前模型中有效。

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