Background: Peptide/protein hormones are stored as amyloids within endocrine secretory granules. Results: Disulfide bond cleavage enhances conformational dynamics and aggregation kinetics in somatostatin-14, resulting in amyloid fibrils with increased resistance to denaturing conditions and decreased reversibility. Conclusion: Disulfide bond could be a key modulating factor in somatostatin-14 amyloid formation associated with secretory granule biogenesis. Significance: Defective disulfide bonding might cause dysregulation of hormone storage/secretion.

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.