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

Istvan Horvath (Institutionen för biologi och bioteknik, Kemisk biologi) ; Pernilla Wittung-Stafshede (Institutionen för biologi och bioteknik, Kemisk biologi)
Proceedings of the National Academy of Sciences of the United States of America (0027-8424). Vol. 113 (2016), 44, p. 12473-12477.
[Artikel, refereegranskad vetenskaplig]

In type-2 diabetes (T2D) and Parkinson's disease (PD), polypeptide assembly into amyloid fibers plays central roles: in PD, alpha-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 proIAPP 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.

Nyckelord: alpha-synuclein, fluorescence, amyloid, atomic force microscopy, amylin



Denna post skapades 2016-11-30. Senast ändrad 2017-03-21.
CPL Pubid: 245742

 

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Institutioner (Chalmers)

Institutionen för biologi och bioteknik, Kemisk biologi

Ämnesområden

Biokemi och molekylärbiologi

Chalmers infrastruktur