INHIBITION OF BETA-AMYLOID CYTOTOXICITY BY MIDKINE

Midkine (MK) is a neurotrophic and angiogenic growth factor whose expr ession occurs mainly in fetus. It was reported that MK was present in senile plaques of Alzheimer's disease (AD). To investigate the role of MK during amyloid plaques formation in AD, we examined the in vitro e ffect of MK on A beta aggregation and A beta-induced cytotoxicity. We found that incubation of MK with A beta resulted in the formation of M K/A beta complexes. The C-terminus of MK (60-121) played a similar rol e as the full length MK in complex formation. This interaction of MK a nd A beta demonstrated significant inhibition on A beta self-aggregati on. MK also inhibited the cytotoxicity of A beta on PC12h cells. These findings suggest that MK protects the cells from A beta-induced cytot oxicity through its complex formation with A beta. MK is probably expr essed to prevent cell death in AD. (C) 1998 Elsevier Science Ireland L td. All rights reserved.