title: 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: Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden.
authors: Istvan
authors: I
authors: Horvath
authors: Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden pernilla.wittung@chalmers.se.
authors: Pernilla
authors: P
authors: Wittung-Stafshede
mesh_terms: D058227:Amyloidogenic Proteins / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000378:metabolism; D018625:Microscopy, Atomic Force; D010300:Parkinson Disease / Q000378:metabolism*; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological; D011485:Protein Binding; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D058227:Amyloidogenic Proteins; D058228:Islet Amyloid Polypeptide; D066329:Protein Aggregates; D051844:alpha-Synuclein
keywords: amylin; amyloid; atomic force microscopy; fluorescence; α-synuclein