Huperzine A enhances the level of secretory amyloid precursor protein and protein kinase C-α in intracerebroventricular β-amyloid-(1-40) infused rats and human embryonic kidney 293 Swedish mutant cells

We examined whether huperzine A (HupA), a promising therapeutic agent for Alzheimer's disease, could alter the processing of amyloid precursor protein (APP) in rats with P-amyloid protein-(1-40) (Abeta(1-40)) infusion into the cerebral ventricle and in human embryonic kidney 293 (HEK293sw) cells. Daily intraperitoneal administration of HupA for 12 consecutive days produced significant reversals of the Abeta(1-40)-induced down-regulation of secretory APP (APPs) and protein kinase C (PKC) in rats. In the HEK293sw cells, the level of APPs was increased significantly with HupA treatment, and there was a similar change in PKCalpha level under the same condition. However, no significant alternations in the levels of PKCdelta and PKCepsilon were found after HupA treatment. These findings suggest that HupA may affect the processing of APP by up-regulating PKC, especially PKCalpha. (C) 2004 Elsevier Ireland Ltd. All rights reserved.