Phosphorylation of Amyloid-β Peptide at Serine 8 Attenuates Its Clearance via Insulin-degrading and Angiotensin-converting Enzymes

Background: Amyloid-beta peptide (A beta) is degraded by different proteases. We recently demonstrated phosphorylation of A beta. Results: Phosphorylation of A beta decreases its clearance by microglial BV-2 cells and selectively inhibits the cleavage by insulin-degrading and angiotensin-converting enzymes. Conclusion: Phosphorylation at Ser-8 negatively regulates A beta degradation. Significance: Phosphorylation could play a dual role in A beta metabolism. It decreases the clearance by microglial cells and also promotes A beta aggregation.