Salvianolic acid B ameliorates Aβ42 toxicity in Aβ42-expressing Drosophila model: behavioral and transcriptomic...

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases worldwide. It is characterized by the accumulation of amyloid-beta (Aβ) plaques in which Aβ42 is the most toxic and aggressive species. This work investigates the possibility of salvianolic acid B (SalB), a natural compound with established neuroprotective activity, to counteract the Aβ42-induced toxicity in a Drosophila melanogaster model of AD. SalB's effect was assessed in the Aβ42-expressing Drosophila model by measuring three major AD-related behavioural symptoms: eye morphology (cytotoxicity), lifespan, and locomotor activity. The eye assay, longevity, and locomotion assays were employed, followed by RNA sequencing (RNA-seq) to identify molecular alterations following SalB treatment. Aβ42 expression in the Aβ42-expressing Drosophila model resulted in deformed eye morphology, reduced lifespan, and motor impairment. Treatment with SalB restored part of eye morphology, extended lifespan, and improved locomotion. RNA-seq revealed differential gene expression in oxidative phosphorylation, glutathione metabolism, and detoxification processes, suggesting the involvement of antioxidant defence in SalB-mediated neuroprotection. These findings indicate that SalB could be therapeutic for AD and other neurodegenerative disorders, possibly through the modulation of oxidative stress against Aβ42 toxicity. Further research is warranted to address its mechanisms and other uses in neurodegenerative therapy.