Cross-talk between amyloidogenic proteins in type-2 diabetes and Parkinson's disease.

Abstract

In type-2 diabetes (T2D) and Parkinson's disease (PD), polypeptide assembly into amyloid fibers plays central roles: in PD, α-synuclein (aS) forms amyloids and in T2D, amylin [islet amyloid polypeptide (IAPP)] forms amyloids. Using a combination of biophysical methods in vitro we have investigated whether aS, IAPP, and unprocessed IAPP, pro-IAPP, polypeptides can cross-react. Whereas IAPP forms amyloids within minutes, aS takes many hours to assemble into amyloids and pro-IAPP aggregates even slower under the same conditions. We discovered that preformed amyloids of pro-IAPP inhibit, whereas IAPP amyloids promote, aS amyloid formation. Amyloids of aS promote pro-IAPP amyloid formation, whereas they inhibit IAPP amyloid formation. In contrast, mixing of IAPP and aS monomers results in coaggregation that is faster than either protein alone; moreover, pro-IAPP can incorporate aS monomers into its amyloid fibers. From this intricate network of cross-reactivity, it is clear that the presence of IAPP can accelerate aS amyloid formation. This observation may explain why T2D patients are susceptible to developing PD.

• Authors: Istvan Horvath, Pernilla Wittung-Stafshede
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 113 Issue 44 Pg. 12473-12477 (11 01 2016) ISSN: 1091-6490 [Electronic] United States
• PMID: 27791129 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloidogenic Proteins
• Islet Amyloid Polypeptide
• Protein Aggregates
• alpha-Synuclein

Topics

• Amyloidogenic Proteins (metabolism)
• Amyloidosis (metabolism)
• Animals
• Diabetes Mellitus, Type 2 (metabolism)
• Humans
• Islet Amyloid Polypeptide (metabolism)
• Microscopy, Atomic Force
• Parkinson Disease (metabolism)
• Protein Aggregates
• Protein Aggregation, Pathological
• Protein Binding
• alpha-Synuclein (metabolism)