fluorescence assay and transmission electron miscroscopy (TEM). We observed that site-specific asparagine deamidation to aspartic acid accelerates amyloid formation, whereas asparagine deamidation to isoaspatic acid perseveres aggregation. The process of fibrillogenesis in absence or in presence of deamidation modifications was also monitored by circular dichroism (CD) spectroscopy and we observed that the conformational transition disordered-to-beta-sheet associated with IAPP/IAPPs deamidated assembly was modulated. Using rat pancreatic beta-cells, we observed that deamidation reaction does not prevent IAPP-induced toxicity. These results show that site-specific asparagine deamidation could potentially play a key role in the etiology of DM-2 by promoting IAPP amyloidogenic cascade and/or by stabilizing the resulting amyloid fibrils.

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