Erdoğan Mehmet Evren, Aydın Seval, Yanar Karolin, Mengi Murat, Kansu Ahmet Doğukan, Cebe Tamer, Belce Ahmet, Çelikten Mert, Çakatay Ufuk
Department of Medical Biochemistry, Cerrahpaşa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Department of Physiology, Cerrahpaşa Faculty of Medicine, İstanbul University, Istanbul, Turkey.
Metab Brain Dis. 2017 Aug;32(4):1017-1031. doi: 10.1007/s11011-017-9983-6. Epub 2017 Mar 15.
While the deterioration of insulin-glucose metabolism (IGM), impaired redox homeostasis (IRH), β-amyloid accumulation was reported in Sporadic Alzheimer's Disease (SAD) model, aforementioned factors related to lipoic acid administration and anthropometric indexes (AIs) are not yet studied with integrative approach. β-amyloid accumulation, redox homeostasis biomarkers and AIs are investigated in SAD model. Streptozotocin-induced inhibition of insulin-signaling cascade but not GLUT-2 and GLUT-3 transporters takes a role in β-amyloid accumulation. Inhibition types are related to IRH in cortex, hippocampus and systemic circulation. Lipoic acid (LA) shows both antioxidant and prooxidant effect according to the anatomical location. LA administration also leads to improved AIs during GLUT-2 inhibition and cortical redox status in GLUT-3 inhibited group. Optimal LA action could be possible if its redox behavior is balanced to antioxidant effect. Diagnostic usage of systemic IRH parameters as biomarkers and their possible correlations with deteriorated IGM should be investigated. Graphical abstract ᅟ.
虽然在散发性阿尔茨海默病(SAD)模型中报道了胰岛素 - 葡萄糖代谢(IGM)恶化、氧化还原稳态受损(IRH)、β - 淀粉样蛋白积累,但上述与硫辛酸给药和人体测量指标(AIs)相关的因素尚未采用综合方法进行研究。在SAD模型中研究了β - 淀粉样蛋白积累、氧化还原稳态生物标志物和AIs。链脲佐菌素诱导的胰岛素信号级联抑制而非GLUT - 2和GLUT - 3转运蛋白在β - 淀粉样蛋白积累中起作用。抑制类型与皮质、海马和体循环中的IRH有关。硫辛酸(LA)根据解剖位置显示出抗氧化和促氧化作用。在GLUT - 2抑制期间,LA给药还导致AIs改善,在GLUT - 3抑制组中改善皮质氧化还原状态。如果LA的氧化还原行为与抗氧化作用达到平衡,则可能实现最佳作用。应研究将全身IRH参数作为生物标志物的诊断用途及其与恶化的IGM的可能相关性。图形摘要ᅟ