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 SiO4(4-) with Al3+ provides the mechanism for this transition. These results provide insight into the role of aluminum in the Alzheimer diseased brain and suggests that investigation of the use of silicates as a therapeutic agent.
Graduate Department of Biochemistry, Brandeis University, Waltham, MA 02254.
G D
GD
Fasman
A
A
Perczel
C D
CD
Moore
D000535:Aluminum / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000818:Animals; D011232:Chemical Precipitation; D002942:Circular Dichroism; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary / Q000187:drug effects*; D051381:Rats; D017640:Silicates / Q000494:pharmacology*; D012995:Solubility; D017186:Titrimetry
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D017640:Silicates; C075222:amyloid beta-protein (1-42); D000535:Aluminum