In:
FEBS Letters, Wiley, Vol. 580, No. 28-29 ( 2006-12-11), p. 6587-6595
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 (CHPNH 2 ) with positive charges under physiological conditions had a greater inhibitory effect than CHP‐nanogels, suggesting the importance of electrostatic interactions between CHPNH 2 and Aβ for inhibiting the formation of fibrils. In addition, CHPNH 2 nanogels protected PC12 cells from Aβ toxicity.
Type of Medium:
Online Resource
ISSN:
0014-5793
,
1873-3468
DOI:
10.1016/j.febslet.2006.11.009
Language:
English
Publisher:
Wiley
Publication Date:
2006
detail.hit.zdb_id:
212746-5
detail.hit.zdb_id:
1460391-3
SSG:
12
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