Although causes of Alzheimer disease are not known yet in a detail, it is suggested that amyloid beta peptides play a key role in the pathogenesis of disease. Toxicity of peptides is probably closely connected with their ability to ologomerize or to form complexes with different endogenous substances. A great attention is now focused on the research od drugs that via binding to amyloid beta peptides can eliminated their toxic effects and that could be applied in Alzheimer disease therapy. E.g., the stereospecific binding to naturally occurring 22R-hydroxy-cholesterol decreases peptide toxicity and enantiomer 22S-hydroxycholesterol is not effective. Naturally occurring and brain-originating 24S-hydroxycholesterol (cerebrosterol) is a very efficient inhibitor of amyloid beta peptide secretion in experiments in vitro. Our previous work indicated the decreased actions of nonaggregated and aggregated peptides when racemic 24-hydroxycholesterol was added and data suggested a formation of the complex as probable. However, interaction mechanisms are not known yet in a detail. (en)
Cíle projektu jsou následující: 1) otestovat účinky L- a D-enantiomerů fragmentu amyloidu beta 1-40 a 24S- a 24R-hydroxycholesterolu, 2) zjistit, zda je interakce mezi přirozeně se vyskytujícím L-fragmentem 1-40 a cerebrosterolem stereospecifická a 3)pokusit se vytvořit počítačový model komplexu.