Nawar_2025_Toxicol.Res.(Camb)_14_tfaf031

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(3) (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, Abeta(1-42), 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. HIGHLIGHTS: Coenzyme Q10 (CoQ10) improved the rats' passive avoidance memory impairment caused by D-gal and AlCl(3). 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 Abeta plaque in the hippocampal neurons of D-Gal and AlCl(3)-treated rats.One promising therapeutic method was the combination of donepezil and CoQ10 therapy.