The Solubilization of Model Alzheimer Tangles: Reversing the β-Sheet Conformation Induced by Aluminum with Silicates

Neurofibrillary tangles are one of two lesions found in the brain of Alzheimer disease victims. With synthetic peptide fragments of human neurofilament NF-M17 (Glu-Glu-Lys-Gly-Lys-Ser-Pro-Val-Pro-Lys-Ser-Pro-Val-Glu-Glu-Lys-Gly, phosphorylated and unphosphorylated), CD studies were done to examine the effect of sodium orthosilicate on the conformational state produced by Al³⁺ on fragments of neuronal proteins. Previous studies had shown a conformational transition from α-helix and random to β-pleated sheet upon addition of Al³⁺ to both phosphorylated and unphosphorylated peptides. If sufficient quantities of Al³⁺ are added, the peptide precipitates from solution. The ability to reverse or slow the progression of aggregation was examined. Al³⁺ binding was reversed with 1-2 molar equivalents of sodium orthosilicate (with respect to Al³⁺), altering the conformation from β-sheet to random coil and resulting in a CD spectrum similar to that of the initial peptide. The tight binding of the SiO^4-_4 with the Al³⁺ provides the mechanism for this transition. These results provide additional information toward understanding the role of aluminum in the Alzheimer diseased brain and suggest the investigation of the possible use of silicates as a therapeutic agent.