Abstract
Amyloid beta (Aβ) is a peptide responsible for the development of Alzheimer's disease (AD). Misfolding and accumulation of endogenous Aβ can lead to neural cell apoptosis through endoplasmic reticulum (ER) stress. Added exogenous Aβ can also result in ER stress, leading to neurotoxicity and apoptosis, which is identical to that caused by the endogenous peptide. We have speculated that the endocytic transport of Aβ causes ER stress and have previously shown that the oxysterol, in particular, 7-ketocholesterol (7-keto) induces more surface interaction between Aβ-42 and Jurkat cells than cholesterol. However, the interaction was not enough to induce intracellular transfer of the peptide. In this study, we investigated the effect of another oxysterol, 25-hydroxycholesterol (25-OH) on the membrane raft-dependent transport of Aβ-42 in Jurkat cells. Interestingly, intracellular transfer of Aβ-42 was observed in the presence of 25-OH only after the inclusion of cholera toxin B subunit (CT-B), a marker used to detect the raft domain. We speculated that 25-OH can induce intracellular movement of Aβ peptides. Furthermore, CT-B together with GM1 provided negative curvature, which resulted in the intracellular transport of Aβ-42. Notably, we used a protofibrillar species of Aβ-42 in this study. We have shown that the transport was microtubule-dependent since it could not be observed in depolymerized microtubules. These results demonstrate that oxysterols and glycosyl chains are important factors affecting intracellular transport. These compounds are also associated with aging and advanced glycation are risk factors for AD. Thus, this study should further understanding of the pathology of AD.