Interactions of Amyloid beta Peptide 1 - 40 and Cerebrosterol
| Název česky | Interakce amyloidu beta 1 - 40 s cerebrosterolem |
|---|---|
| Autoři | |
| Rok publikování | 2012 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Neurochemical Research |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | http://www.springerlink.com/content/t5tm1222071x5214/ |
| Doi | http://dx.doi.org/10.1007/s11064-011-0650-8 |
| Obor | Neurologie, neurochirurgie, neurovědy |
| Klíčová slova | Stereospecificity; Amyloid beta peptide; Oxysterol; Alzheimer disease |
| Přiložené soubory | |
| Popis | Amyloid beta peptides appear to play a role in physiological processes; however, they are also involved in the pathogenesis of Alzheimer disease. Their actions under normal conditions are probably mediated by soluble monomeric L-isoforms at low concentrations, perhaps via highly specific interactions. On the contrary, toxic effects of aggregated natural L-isoforms/synthetic D-isoforms on membranes are very similar, but synthetic reverse/random L-isoforms without pronounced aggregation properties are not toxic. Our previous work reported interactions of non-aggregated/aggregated L-isoforms of amyloid b peptides 1–40/1–42 with racemic 24-hydroxycholesterol. In this study, stereospecificity in the interactions of natural 24(S)hydroxycholesterol (cerebrosterol) or synthetic 24(R)hydroxycholesterol with soluble fragment 1–40 was evaluated by means of an in vitro test based on increased vulnerability of the hemicholinium-3 sensitive high-affinity choline uptake system in rat hippocampal cholesteroldepleted synaptosomes to the actions of amyloid beta; computational simulations were also performed. Our results suggest that: (1) 24(S)hydroxycholesterol interacts with L-peptide 1–40 but not with the reverse L-peptide 40–1, (2) 24(R)hydroxycholesterol does not interact with L-peptide 1–40 or reverse 40–1, and (3) both enantiomers can probably interact with D-peptide 1–40. Therefore, the binding of 24(S)hydroxycholesterol is not fully stereospecific and the interaction could not reflect a physiological mechanism. Data from the computational simulation indicate that the hydrophobic core of the amyloid beta molecule interacts with the hydrophobic part of 24(S)hydroxycholesterol, but no hydrogen bonds with high stability were found. Using this procedure, globular amyloid b could retain 24(S)hydroxycholesterol and thus contribute to its pathological accumulation in the brains of patients with Alzheimer disease. |
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