Understanding the Mechanism of Somatostatin-14 Amyloid Formation In Vitro

Abstract

destabilizing conditions, WT myoc-OLF has a distinct non-native structure capable of forming amyloid fibrils. In the case of disease-causing myocilin variants, this non-native structure is accessible under physiological conditions, leading to accelerated fibril growth. Building on the hypothesis that partial unfolding of myoc-OLF is necessary for fibril growth, this study also investigates the structural and biophysical effects of adding stabilizing agents, such as osmolytes and Ca 2þ , to the myoc-OLF domain as a strategy to prevent myoc-OLF amyloid aggregation. The results of this study suggest a novel proteinbased hypothesis for glaucoma pathogenesis and the need for further testing in a clinical setting.

Functional Amyloids and their Possible Influence on Alzheimer Disease

“…Once the process has been initiated, nascent aggregation states might be further condensed by the high hormone concentration and the more acidic pH present in secretory granules. In the process, which is facilitated by the presence of heparin 161 , amyloid aggregates somehow attract membrane lipids to surround the hormone aggregates, thereby forming the nascent granule, which subsequently is severed from the Golgi cisterna. 162 Once formed, secretory granules represent a stable depot for long-term storage of peptide hormones.…”