Selective inhibition of Abeta fibril formation.

摘要: Abstract We describe here an inhibitor of in vitro fibril formation, hexadecyl-N-methylpiperidinium (HMP) bromide, which is selective for the Alzheimer's disease peptide Aβ. At 10 μM, its IC inhibiting Aβ aggregation at pH 5.8, HMP bromide does not inhibit formation by other amyloidogenic polypeptides nor it affect folding stability β-sheet-rich immunoglobulin VL domain REI. In addition, small structural modifications reduce or eliminate ability to 5.8 These indications specificity, plus molecule concentrations almost order magnitude below critical micelle concentration, suggest a mechanism inhibition than micellar solubilization required approximately 1:1 stoichiometry effective 5.8. Although stoichiometric amounts with respect total 7.4, incapable, lower concentrations, blocking seeding added fibrils. The results existence binding surface on capable amphipathic molecules such as and which, when occupied, precludes assembly into amyloid Molecules that bind this site high specificity may prove be useful therapeutic agents preventing retarding cerebral plaque implicated pathology.