Inhibition of insulin amyloid formation by small stress molecules.
Amyloidogenic proteins undergo an alternative folding pathway under stressful conditions leading to formation of fibrils having cross beta-sheet structure, which is the hallmark of many neurodegenerative diseases. As a means of surviving against external stress, on the other hand, many microorganisms accumulate small stress molecules to prevent abnormal protein folding and to contribute to protein stability, which hints at the efficacy of the solutes against amyloid formation. The current work demonstrates the effectiveness of small stress molecules such as ectoine, betaine, trehalose, and citrulline on inhibition of insulin amyloid formation in vitro. The inhibitory effects were analyzed by thioflavin T-induced fluorescence, circular dichroism, and atomic force microscopy. This report suggests that naturally occurring small molecules may serve a function that is typically fulfilled by protein chaperones, and it provides a hint for designing inhibitors against amyloid formation associated with neurodegenerative disorders.
Arora
Anubhav
A
Department of Chemical and Materials Engineering, Arizona State University, Tempe, AZ 85287, USA.
Ha
Chanki
C
Park
Chan Beum
CB
D000599:Amino Acids, Diamino / Q000494:pharmacology; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000686:Amyloidosis / Q000517:prevention & control; D000818:Animals; D001622:Betaine / Q000494:pharmacology; D002417:Cattle; D002956:Citrulline / Q000494:pharmacology; D007328:Insulin / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D018625:Microscopy, Atomic Force; D013057:Spectrum Analysis; D013312:Stress, Physiological / Q000378:metabolism*; D014199:Trehalose / Q000494:pharmacology
D000599:Amino Acids, Diamino; D000682:Amyloid; D007328:Insulin; D002956:Citrulline; D001622:Betaine; C045628:ectoine; D014199:Trehalose