Thymoquinone as a potential therapeutic for Alzheimer’s disease in transgenic Drosophila melanogaster model

Abstract

Alzheimer’s disease (AD) is one of the most common forms of dementia. Cognitive dysfunction and memory loss are the two main clinical symptoms of AD. Drosophila melanogaster models of AD, which are based on overexpression of human amyloid β (Aβ) or human tau (hTau) protein, have been used to study the mechanism underlying AD and to screen potential therapeutic compounds. Drugs that are currently available for AD provide only symptomatic relief. Huge unmet medical needs exists to slow, stop, or reverse the progression of AD. Thymoquinone (TQ) is an active ingredient isolated from Nigella sativa (NS) and possesses various pharmacological activities, and it is also a potential neuropharmacological agent. The current study was performed to investigate the effect of dietary administration of TQ at concentrations of 12.5 μM and 25 μM for 15 and 30 days on biochemical and behavioral parameters, gene, and protein expression of hTau, using Drosophila models of AD. Transgenic Drosophila models exhibiting pan-neuronal and eye-specific expression of hTau were generated using the GAL4/UAS system. Treatment with TQ at both concentrations resulted in a significant increase in behavioral activity, a significant reduction in the amount of reactive oxygen species (ROS), and restoration of depleted superoxide dismutase (SOD) and acetylcholine esterase (AChE) activities. A significant decrease in gene and protein expression of hTau was also observed at the molecular level for both concentrations of TQ. Therefore, TQ has the potential to be investigated as a potential therapeutic phytochemical for the treatment of AD in future studies.