Activation of microglial cells by PrP and beta-amyloid fragments raises intracellular calcium through L-type voltage sensitive calcium channels

The prion protein (PrP) and the amyloid beta (A beta) precursor protein (AP P) are two normal proteins constitutively synthesised in human brain. An al tered form of PrP accumulates in Creutzfeldt-Jakob disease, while A beta is involved in the pathogenesis of Alzheimer's disease. Synthetic fragments o f both proteins, PrP106-126 and beta 25-35 (beta 25-35), have been demonstr ated to induce neurodegeneration and microglia activation. This study was u ndertaken to compare PrP106-126 and beta 25-35 capability of activating hum an resting micro lial cells. Our results show that both peptides are able t o induce microglial activation and to elicit an increase in [Ca2+](i) level s in cells loaded with calcium-green 1. inhibitors of L-type voltage-sensit ive calcium channels (verapnmil, nifedipine and diltiazem) prevented the in crease in [Ca2+](i) concentration as observed after treatment with PrP106- 126 and beta 25-35, thus indicating a transmembrane calcium influx through these channels. In addition, verapamil abolished the proliferative effect o f both PrP106-126 and beta 25-35. (C) 1999 Published by Elsevier Science B. V. All rights reserved.