Renin inhibitor aliskiren exerts neuroprotection against amyloid beta-peptide toxicity in rat cortical neurons

Accumulation of amyloid beta-peptide (A beta) in senile plaques, a pathological hallmark of Alzheimer's disease (AD), has been implicated in neuronal degeneration. Renin-angiotensin system (RAS) blockers, including the renin inhibitor aliskiren, are a group of clinically relevant anti-hypertensive agents. The present study was initiated to investigate whether aliskiren may modulate A beta neurotoxicity as an additional function aside from its established property of lowering blood pressure. We found aliskiren conferred neuronal resistance to A beta toxicity in primary rat cortical cultures. Moreover, both A beta 25-35 and A beta 1-42 induced renin expression in cortical neurons; in parallel, a heightened expression of renin was detected in the cerebral cortices of 9-month-old AD transgenic mice. Notably, aliskiren blocked A beta-mediated neuronal induction of renin. We therefore concluded that aliskiren may carry neuroprotective action against A beta toxicity. Furthermore, the aliskiren effects may involve downregulation of renin expression induced by A beta. (C) 2012 Elsevier Ltd. All rights reserved.