SOLUBILIZATION OF BETA-AMYLOID-(1-42)-PEPTIDE - REVERSING THE BETA-SHEET CONFORMATION INDUCED BY ALUMINUM WITH SILICATES

Plaques are one of the two lesions found in the brain of patients with Alzheimer disease. Using a synthetic peptide corresponding to rat beta-amyloid-(1-42) (beta A4), circular dichroism (CD) analyses were performed to examine the effect of Na4SiO4 on the conformational state produced by Al3+. A previous study on fragments of neuronal proteins involved in tangle formation had shown a conformational transition from a beta-pleated sheet to a soluble random coil upon addition of Na4SiO4. In the present study, CD measurements showed that the beta-pleated sheet conformation of beta A4 induced by Al3+ was reversed to the random coil soluble form by the addition of Na4SiO4. The tight binding of SiO44- with Al3+ provides the mechanism for this transition. These results provide insight into the role of aluminum in the Alzheimer diseased brain and suggests the investigation of the use of silicates as a therapeutic agent.