Formation of non-toxic Aß fibrils by small heat shock protein under heat-stress conditions.

Biochemical and biophysical research communications

PubMedID: 23261462

Sakono M, Utsumi A, Zako T, Abe T, Yohda M, Maeda M. Formation of non-toxic Aß fibrils by small heat shock protein under heat-stress conditions. Biochem Biophys Res Commun. 2013;430(4):1259-64.
Small heat shock protein (sHsp) is a molecular chaperone with a conserved alpha-crystallin domain that can prevent protein aggregation. It has been shown that sHsps exist as oligomers (12-40 mer) and their dissociation into small dimers or oligomers is functionally important. Since several sHsps are upregulated and co-localized with amyloid-ß (Aß) in senile plaques of patients with Alzheimer's disease (AD), sHsps are thought to be involved in AD. Previous studies have also shown that sHsp can prevent Aß aggregation in vitro. However, it remains unclear how the quaternary structure of sHsp influences Aß aggregation. In this study, we report for the first time the effect of the quaternary structure of sHsp on Aß aggregation using sHsp from the fission yeast Schizosaccharomyces pombe (SpHsp16.0) showing a clear temperature-dependent structural transition between an oligomer (30 °C) and dimer (50 °C) state. Aß aggregation was inhibited by the oligomeric form of SpHsp16.0. In contrast, amyloid fibrils were formed in the presence of dimeric SpHsp16.0. Interestingly, these amyloid fibrils consisted of both Aß and SpHsp16.0 and showed a low ThT intensity and low cytotoxicity due to their low binding affinity to the cell surface. These results suggest the formation of novel fibrillar Aß amyloid with different characteristics from that of the authentic Aß amyloid fibrils formed in the absence of sHsp. Our results also suggest the potential protective role of sHsp in AD under stress conditions.