Lee Hyun-Ju, Jeong Ha-Ram, Park Jin-Hee, Hoe Hyang-Sook
Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61 Cheomdan-ro, Dong-gu, Daegu 41068, Korea.
Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science & Technology, Daegu 42988, Korea.
Biology (Basel). 2021 Sep 19;10(9):938. doi: 10.3390/biology10090938.
The coenzyme Q10 analogue idebenone is an FDA-approved antioxidant that can cross the blood-brain barrier (BBB). The effects of idebenone on the pathology of Alzheimer's disease (AD) and the underlying molecular mechanisms have not been comprehensively investigated. Here, we examined the impact of idebenone treatment on AD pathology in 5xFAD mice, a model of AD. Idebenone significantly downregulated Aβ plaque number via multi-directional pathways in this model. Specifically, idebenone reduced the RAGE/caspase-3 signaling pathway and increased levels of the Aβ degradation enzyme NEP and α-secretase ADAM17 in 5xFAD mice. Importantly, idebenone significantly suppressed tau kinase p-GSK3β levels, thereby inhibiting tau hyperphosphorylation at Thr231 and total tau levels in 5xFAD mice. Taken together, the present study indicates that idebenone modulates amyloidopathy and tauopathy in 5xFAD mice, suggesting therapeutic potential for AD.
辅酶Q10类似物艾地苯醌是一种经美国食品药品监督管理局（FDA）批准的抗氧化剂，能够穿过血脑屏障（BBB）。艾地苯醌对阿尔茨海默病（AD）病理及潜在分子机制的影响尚未得到全面研究。在此，我们研究了艾地苯醌治疗对AD模型5xFAD小鼠AD病理的影响。在该模型中，艾地苯醌通过多向途径显著下调Aβ斑块数量。具体而言，艾地苯醌降低了5xFAD小鼠中的RAGE/半胱天冬酶-3信号通路，并提高了Aβ降解酶NEP和α-分泌酶ADAM17的水平。重要的是，艾地苯醌显著抑制了tau激酶p-GSK3β的水平，从而抑制了5xFAD小鼠中Thr231位点tau的过度磷酸化以及总tau水平。综上所述，本研究表明艾地苯醌可调节5xFAD小鼠的淀粉样病变和tau病变，提示其对AD具有治疗潜力。
