Pharmacological Insights into Statins' Role in Neurological Disorders

Abstract

Statins, widely used as lipid-lowering agents, have been shown to exert multiple beneficial effects through mechanisms independent of cholesterol metabolism. These pleiotropic effects are attributed to the inhibition of isoprenoid intermediate synthesis within the mevalonate pathway, leading to the suppression of small GTP-binding protein signaling. Statins enhance endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) bioavailability, while reducing reactive oxygen species (ROS) levels. They inhibit NADPH oxidase activity and expression, a primary source of superoxide generation in vascular tissues and the central nervous system. Statins also upregulate eNOS expression and activity, improve its enzymatic coupling, and increase NO bioavailability. Additionally, statins act as matrix metalloproteinase (MMP) inhibitors, reducing MMP production and activity, which is associated with various neurological disorders. Growing evidence suggests potential therapeutic applications for statins in stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and primary brain tumors. However, the efficacy and safety of statins in these neurological conditions require further confirmation through randomized clinical trials. While statins are generally well-tolerated, potential adverse effects, such as myopathy and liver toxicity, should be monitored. The pleiotropic effects of statins highlight their promise as neuroprotective agents, warranting further research to elucidate their mechanisms of action and therapeutic potential in neurological disorders.