Nawar Nagat F, Beltagy Doha M, Tousson Ehab, El-Keey Mai M, Mohamed Tarek M
Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, 31527, Egypt.
Division of Biochemistry, Department of Chemistry, Faculty of Science, Damanhour University, 22514, Egypt.
Toxicol Res (Camb). 2025 Mar 5;14(2):tfaf031. doi: 10.1093/toxres/tfaf031. eCollection 2025 Apr.
Alzheimer's disease (ad) is the most progressive form of neurodegenerative disease resulting in cognitive and non-cognitive deficits. Coenzyme Q10 (CoQ10) is an anti-inflammatory and anti-oxidative stress supplement that can improve inflammation and oxidative stress associated with ad. This study aimed to explore the protective potential of coenzyme Q10 (CoQ10). It also sought to uncover any synergistic effects when combined with donepezil, an acetylcholinesterase inhibitor, in treating Alzheimer's disease in rats, focusing on the modulation of the TLR-4/MAPK pathway and regulation of microRNA. The experiment involved seventy rats categorized into different groups: control, Reference group (donepezil 10 mg/kg/P.O.), CoQ10 alone (1,200 mg/kg/P.O.), ad-model (D-galactose (120 mg/kg/i.p) + Alcl (50 mg/kg/P.O.)), donepezil co-treatment, CoQ10 co-treatment, and CoQ10 + donepezil co-treatment. Behavioral parameter was defined using the Morris-Maze test (MMT) and various assessments, such as GABA, oxidative stress, Aβ, ion homeostasis, toll-like receptor-4 (TLR-4), mitogen-activated protein kinase-1 (MAPK-1), micro-RNA (mir-106b, mir-107, and mir-9) were measured. Immunohistological staining was used to assess structural abnormalities in hippocampus. CoQ10 treatment demonstrated memory improvement, enhanced locomotion, and increased neuronal differentiation, mainly through the activation of the TLR-4/MAPK pathway and regulation of mir-106b, mir-107, and mir-9.
Coenzyme Q10 (CoQ10) improved the rats' passive avoidance memory impairment caused by D-gal and AlCl. ad led to the alteration of the TLR-4/MAPK pathways.CoQ10 as a protective agent, diminishes oxidative burden, improve ion homeostasis.CoQ10 counteracts Alzheimer's disease by enhancing neurotransmitter parameter and regulating the MicroRNA.CoQ10 lowered accumulation of Aβ plaque in the hippocampal neurons of D-Gal and AlCl-treated rats.One promising therapeutic method was the combination of donepezil and CoQ10 therapy.
阿尔茨海默病（AD）是神经退行性疾病中最具进展性的形式，会导致认知和非认知功能缺陷。辅酶Q10（CoQ10）是一种抗炎和抗氧化应激补充剂，可改善与AD相关的炎症和氧化应激。本研究旨在探索辅酶Q10（CoQ10）的保护潜力。它还试图揭示与乙酰胆碱酯酶抑制剂多奈哌齐联合使用时在治疗大鼠阿尔茨海默病中的协同效应，重点关注Toll样受体4（TLR-4）/丝裂原活化蛋白激酶（MAPK）途径的调节和微小RNA的调控。实验涉及70只大鼠，分为不同组：对照组、参考组（多奈哌齐10mg/kg/口服）、单独使用CoQ10组（1200mg/kg/口服）、AD模型组（D-半乳糖（120mg/kg/腹腔注射）+氯化铝（50mg/kg/口服））、多奈哌齐联合治疗组、CoQ10联合治疗组以及CoQ10+多奈哌齐联合治疗组。行为参数通过莫里斯水迷宫试验（MMT）和各种评估来定义，如γ-氨基丁酸（GABA）、氧化应激、β-淀粉样蛋白（Aβ）、离子稳态、Toll样受体4（TLR-4）、丝裂原活化蛋白激酶1（MAPK-1）、微小RNA（mir-106b、mir-107和mir-9）等指标均进行了测量。免疫组织化学染色用于评估海马体的结构异常。CoQ10治疗主要通过激活TLR-4/MAPK途径以及调控mir-106b、mir-107和mir-9，表现出记忆改善、运动增强和神经元分化增加。
辅酶Q10（CoQ10）改善了由D-半乳糖和氯化铝引起的大鼠被动回避记忆障碍。AD导致TLR-4/MAPK途径改变。CoQ10作为一种保护剂，减轻氧化负担，改善离子稳态。CoQ10通过增强神经递质参数和调控微小RNA来对抗阿尔茨海默病。CoQ10降低了D-半乳糖和氯化铝处理的大鼠海马神经元中Aβ斑块的积累。一种有前景的治疗方法是多奈哌齐和CoQ10联合治疗。
