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- Title
Inhibition of the formation of amyloid β-protein fibrils using biocompatible nanogels as artificial chaperones
- Authors
Ikeda, Keisuke; Okada, Takuma; Sawada, Shin-ichi; Akiyoshi, Kazunari; Matsuzaki, Katsumi
- Abstract
Abstract: The formation of fibrils by amyloid β-protein (Aβ) is considered as a key step in the pathology of Alzheimer’s disease (AD). Inhibiting the aggregation of Aβ is a promising approach for AD therapy. In this study, we used biocompatible nanogels composed of a polysaccharide pullulan backbone with hydrophobic cholesterol moieties (cholesterol-bearing pullulan, CHP) as artificial chaperones to inhibit the formation of Aβ-(1–42) fibrils with marked amyloidgenic activity and cytotoxicity. The CHP-nanogels incorporated up to 6–8 Aβ-(1–42) molecules per particle and induced a change in the conformation of Aβ from a random coil to α-helix- or β-sheet-rich structure. This structure was stable even after a 24-h incubation at 37°C and the aggregation of Aβ-(1–42) was suppressed. Furthermore, the dissociation of the nanogels caused by the addition of methyl-β-cyclodextrin released monomeric Aβ molecules. Nanogels composed of amino-group-modified CHP (CHPNH2) with positive charges under physiological conditions had a greater inhibitory effect than CHP-nanogels, suggesting the importance of electrostatic interactions between CHPNH2 and Aβ for inhibiting the formation of fibrils. In addition, CHPNH2 nanogels protected PC12 cells from Aβ toxicity.
- Subjects
ISOPENTENOIDS; CHOLESTEROL; GLYCOPROTEINS; GEL permeation chromatography
- Publication
FEBS Letters, 2006, Vol 580, Issue 28/29, p6587
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2006.11.009