Statins potentiate caspase-3 activity in immortalized murine neurons

Statins are lipid-lowering drugs that have been shown to reduce atherosclerotic cardiovascular morbidity and mortality. However, there is growing evidence from epidemiological studies that long-term treatment with statins has unwanted effects on extrahepatic tissue and increases the risk for neuropathy. To investigate underlying molecular mechanisms we analyzed whether statins influence the activity of caspase-3 in immortalized neurons. Lovastatin and mevastatin are not able to activate caspase-3 but they strongly potentiate its activity when apoptotic signal transduction is initiated by staurosporine. The increase in caspase-3 activity after coincubation with statins and staurosporine was paralleled by an increase in the protein level of the pro-apoptotic GTPase RhoB. Our data provide evidence that statins enhance neuronal apoptosis and therefore give reasons for a careful evaluation when patients with neurological diseases are treated with these drugs.