Dipyridamole for tracking amyloidogenic proteins aggregation and enhancing polyubiquitination

• Published in: Archives of biochemistry and biophysics Vol. 728; p. 109354
• Main Authors: Laneri, Francesca, García-Viñuales, Sara, Lanza, Valeria, Licciardello, Nadia, Milardi, Danilo, Sortino, Salvatore, Grasso, Giuseppe
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 15.10.2022
• Subjects: Aggregation; Amylin; Amyloid; Fluorescence; Insulin; Ubiquitin; Ubiquitin; ThT; AD; HFIP; DMSO; Aβ40; Amylin; T2D; Fluorescence; E1; DP; Insulin; Ub; E2; E3; Aggregation; UPS; Amyloid; hIAPP; UBE1; HRI
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2022.109354

Dipyridamole is currently used as a medication that inhibits blood clot formation and it is also investigated in the context of neurodegenerative and other amyloid related diseases. Here, we propose this molecule as a new diagnostic tool to follow the aggregation properties of three different amyloidogenic proteins tested (insulin, amylin and amyloid β peptide 1–40). Results show that dipyridamole is sensitive to early stage amyloid formation undetected by thioflavin T, giving a different response for the aggregation of the three different proteins. In addition, we show that dipyridamole is also able to enhance ubiquitin chain growth, paving the way to its potential application as therapeutic agent in neurodegenerative diseases. [Display omitted] •Dipyridamole catalyzes UBE1-mediated Ub activation.•It detects early stage amylin aggregates invisible to thioflavin T.•It could be used as a theranostic agent for amyloidogenic proteins.