The binding of pullulan modified cholesteryl nanogels to Abeta oligomers and their suppression of cytotoxicity.
Among various hydrogels able to form monodisperse and stable nanoparticles (20-30 nm) are those with pullulan-bearing cholesteryl moieties (CHP). These nanoparticles can interact with soluble proteins through hydrophobic bonding. The objectives of this study were to investigate whether CHP nanogels would interact with oligomeric forms of the 42 amino acid variant of beta-amyloid (Abeta(1-42)) and if the formation of CHP-Abeta(1-42) oligomer entities will reduce cytotoxicity of Abeta(1-42) in primary cortical cells and microglial (N9) cells. By employing fluorescent CHP analogs with different charges we provide evidence that, (i) both neutral and positively charged CHP nanoparticles interact with Abeta(1-42) monomers and oligomers, (ii) neutral CHP is non-toxic, but positively charged derivatives (CHPNH2) are toxic, particularly in primary cortical cultures, and (iii) binding of both monomeric and oligomeric Abeta(1-42) to CHP significantly reduces Abeta(1-42) toxicity in both the primary cortical and microglial cells. These results suggest that CHP nanogels could provide a valid complementary approach to antibody immunotherapy in neurological disorders characterized by the formation of soluble toxic aggregates, such as those in Alzheimer's disease (AD).
Boridy
Sebastien
S
Department of Pharmacology and Therapeutics, McGill University, McIntyre Medical Sciences Building, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada.
Takahashi
Haruko
H
Akiyoshi
Kazunari
K
Maysinger
Dusica
D
D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000737:chemistry* / Q000494:pharmacology*; D005782:Gels / Q000737:chemistry*; D005936:Glucans / Q000737:chemistry* / Q000494:pharmacology*; D008422:Materials Testing; D051379:Mice; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding
D016229:Amyloid beta-Peptides; D001672:Biocompatible Materials; D005782:Gels; D005936:Glucans; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C009109:pullulan; D002784:Cholesterol