Substituted Organosiloxanes as Potential Therapeutics for Treatment and Prevention of Neurodegenerative Diseases

Abstract

Extensive testing of hydrolysates of commercially available organosilanes has identified a number of bifunctional organosiloxane compounds that show potential as therapeutics for treatment of diseases characterized by amyloid deposition such as Alzheimer's disease (AD). All of these compounds protect from and/or reverse the metal-induced aggregation of amyloid Aβ(1–42) peptide in dynamic light scattering (DLS) assays in trifluoroethanol (TFE) solutions, protect from and/or reverse the metal-induced loss of α-helical structure in TFE solutions of amyloid Aβ(1–42) as measured by circular dichroism (CD), and are able to cross blood-brain barrier models at rates above background using Caco-2 and MDCK cell permeation assays. Based on these studies, we conclude that members of this class of bifunctional organosiloxanes are promising candidates for testing in treatment and/or prevention of AD and other diseases characterized by amyloid deposition.