HMGCR Inhibitor Restores Mitochondrial Dynamics by Regulating Signaling Cascades in a Rodent Alzheimer's Disease Model.

ABSTRACT

Atorvastatin an HMGCR inhibitor may play a role in enhancing spatial and long-term memory and combating anxious behavior deficits induced by Aß1-42. Behavioral deficit studies, immunoblotting for the antioxidant/apoptotic protein expression, flow cytometry (FACS) for mitochondrial ROS, membrane potential (▲ψm), and histopathological alterations were performed against Aß1-42 toxicity. Aß1-42 was infused directly into the brain through i.c.v for the establishment of the AD model. Atorvastatin (ATOR) was administered orally and was used to treat AD in adult male Wistar rats aged between 200 and 250 g. We confirmed that ATOR administration significantly attenuates the Aß1-42-induced cognitive decline targeted mitochondrial-mediated age-dependent disease progression. Nrf2 stabilizes to interact SOD2 antioxidant enzyme, allowing transcriptional activity by the steep increase in ▲ψm and a reduction in ROS by activating mitochondrial superoxide scavenger and Nrf2-dependent pathway. These findings confirmed that ATOR has the potential efficacy to modulate the interference in cognitive decline induced by Aß1-42.