?-Synuclein promotes IAPP fibril formation in vitro and ?-cell amyloid formation in vivo in mice.

ABSTRACT: Type 2 diabetes (T2D), alike Parkinson's disease (PD), belongs to the group of protein misfolding diseases (PMDs), which share aggregation of misfolded proteins as a hallmark. Although the major aggregating peptide in ?-cells of T2D patients is Islet Amyloid Polypeptide (IAPP), alpha-synuclein (?Syn), the aggregating peptide in substantia nigra neurons of PD patients, is expressed also in ?-cells. Here we show that ?Syn, encoded by Snca, is a component of amyloid extracted from pancreas of transgenic mice overexpressing human IAPP (denoted hIAPPtg mice) and from islets of T2D individuals. Notably, ?Syn dose-dependently promoted IAPP fibril formation in vitro and tail-vein injection of ?Syn in hIAPPtg mice enhanced ?-cell amyloid formation in vivo whereas ?-cell amyloid formation was reduced in hIAPPtg mice on a Snca -/- background. Taken together, our findings provide evidence that ?Syn and IAPP co-aggregate both in vitro and in vivo, suggesting a role for ?Syn in ?-cell amyloid formation.

SUBMITTER: Mucibabic M 

PROVIDER: S-EPMC7686322 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature