Carnosic acid ameliorated Aβ-mediated (amyloid-β peptide) toxicity, cholinergic dysfunction and mitochondrial defect in of Alzheimer's Model.

Amyloid-β peptide (Aβ)-induced cholinergic system and mitochondrial dysfunction are major risk factors for Alzheimer's disease (AD). Our previous studies found that carnosic acid (CA), an important polyphenol antioxidant, could significantly delay Aβ-mediated acute paralysis. However, many details and underlying mechanisms of CA's neuroprotection against Aβ-induced cholinergic system defects and mitochondrial dysfunction remain unclear. Herein, we deeply investigated the effects and the possible mechanisms of CA-mediated protection against Aβ toxicity through several AD strains. The results showed CA delayed age-related paralysis and Aβ deposition, and significantly protected neurons from Aβ-induced toxicity. CA might downgrade the expression of and genes, and upregulate and genes to inhibit acetylcholinesterase activity and relieve Aβ-caused cholinergic system defects. Furthermore, CA might also ameliorate Aβ-induced mitochondrial imbalance and oxidative stress through up-regulating the expression of , , , and genes. The enhancements of the cholinergic system and mitochondrial function might be the reasons for the amelioration of Aβ-mediated toxicity and Aβ aggregation mediated by CA. These findings have helped us to understand the CA anti-Aβ activity in and the potential mechanism of action.