| First Author | Mucibabic M | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 20438 |
| PubMed ID | 33235246 | Mgi Jnum | J:299713 |
| Mgi Id | MGI:6491070 | Doi | 10.1038/s41598-020-77409-z |
| Citation | Mucibabic M, et al. (2020) alpha-Synuclein promotes IAPP fibril formation in vitro and beta-cell amyloid formation in vivo in mice. Sci Rep 10(1):20438 |
| abstractText | 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 beta-cells of T2D patients is Islet Amyloid Polypeptide (IAPP), alpha-synuclein (alphaSyn), the aggregating peptide in substantia nigra neurons of PD patients, is expressed also in beta-cells. Here we show that alphaSyn, 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, alphaSyn dose-dependently promoted IAPP fibril formation in vitro and tail-vein injection of alphaSyn in hIAPPtg mice enhanced beta-cell amyloid formation in vivo whereas beta-cell amyloid formation was reduced in hIAPPtg mice on a Snca (-/-) background. Taken together, our findings provide evidence that alphaSyn and IAPP co-aggregate both in vitro and in vivo, suggesting a role for alphaSyn in beta-cell amyloid formation. |
