LAUSR

The impairment of amyloid formation is associated with Parkinson disease (PD) and type 2 diabetes (T2D) in which the primary pathological characteristics are assembly of asynuclein into amyloid fiber and islet amyloid polypeptide (IAPP) formation in pancreatic b-cells, respectively. Horvath and Wittung-Stafshede tried to shed light on the crossreactivity between amyloid formation in PD and T2D by in vitro measurement of a-synuclein, IAPP, and pro-IAPP. The authors harbored 3 steps of biophysical in vitro methods to determine the fact that various peptides are in contact with each other in PD triggered by T2D pathogenesis. The results of individual protein aggregation reactions showed that larger a-synuclein amyloids may be assemblies of more than 1 a-synuclein proto-fibril. In all 3 cases (a-synuclein, IAPP, and pro-IAPP), preformed amyloid fiber seeds sped up the aggregation of monomers of the same protein. The cross-seeding of amyloid formation was studied and showed that preformed IAPP and a-synuclein amyloids seeds sped up a-synuclein amyloid and pro-IAPP formation, respectively, and preformed a-synuclein and pro-IAPP amyloid seeds inhibited the normal aggregation reaction of IAPP amyloid and a-synuclein amyloid, respectively. Atomic force microscopy images showed that the mixtures made by coaggregation of a-synuclein and pro-IAPP describe thicker fibrils in comparison with pro-IAPP alone. The pro-IAPP monomers inhibited a-synuclein aggregation in a concentration-dependent manner. The results contrasted when a-synuclein monomers were added to high concentrations of pro-IAPP; in such cases, a-synuclein monomers became incorporated into the pro-IAPP amyloids without impacting formation speed but allowing for increased thioflavin T emission. The differences in thickness and fragility together with the changed reaction kinetics imply that coassembled amyloids were formed between a-synuclein and IAPP. The majority of studies so far considered the individual disease-specific peptides. The authors in the present study shed light on how the interactions of peptides associated with different amyloid diseases may intermediate amyloid formation pathogenicity. In conclusion, the putative cross-reaction between a-synuclein and processed or unprocessed IAPP has been addressed in this survey for the first time, notably, that a-synuclein aggregation could be elevated by IAPP protein (both as monomer and amyloid seed). This result presents a likely explanation for why patients with T2D are more predisposed to PD, whereas PD patients are not prone to T2D by IAPP amyloid formation inhibition caused by a-synuclein amyloid aggregation.