ATP-independent inhibition of amyloid beta fibrillation by the endoplasmic reticulum resident molecular chaperone GRP78.

Neuronal cell death induced by an accumulation of amyloid beta (Aß) peptides, which are pathogenic molecules for Alzheimer's disease, is closely related with endoplasmic reticulum (ER) stress. In the ER stress condition, part of the ER resident chaperones is known to be translocated to another cellular location, such as the cell surface. The ER chaperone 78-kDa glucose-regulated protein (GRP78), which shows ATP-dependent chaperone activity, also shows translocation to the cell surface. In this study, we examined the influence of GRP78 on Aß fibrillation in the presence or absence of ATP. We revealed that a small amount of GRP78 effectively inhibited fibrillation of Aß fragments. Intriguingly, the fibrillation inhibition by GRP78 was confirmed in the absence of ATP, suggesting GRP78 exhibited ATP-independent interaction with Aß fragments.