Dipyridamole for tracking amyloidogenic proteins aggregation and enhancing polyubiquitination

Francesca Laneri; Sara García-Viñuales; Valeria Lanza; Nadia Licciardello; Danilo Milardi; Salvatore Sortino; Giuseppe Grasso

doi:10.1016/j.abb.2022.109354

Dipyridamole for tracking amyloidogenic proteins aggregation and enhancing polyubiquitination

Arch Biochem Biophys. 2022 Oct 15:728:109354. doi: 10.1016/j.abb.2022.109354. Epub 2022 Jul 19.

Authors

Francesca Laneri¹, Sara García-Viñuales², Valeria Lanza², Nadia Licciardello³, Danilo Milardi⁴, Salvatore Sortino⁵, Giuseppe Grasso⁶

Affiliations

¹ Department of Chemical Sciences, University of Catania, I-95125, Catania, Italy; PhotoChemLab, Department of Drug and Health Sciences, University of Catania, I-95125, Catania, Italy.
² Istituto di Cristallografia, Consiglio Nazionale delle Ricerche, I-95126, Catania, Italy.
³ PhotoChemLab, Department of Drug and Health Sciences, University of Catania, I-95125, Catania, Italy.
⁴ Istituto di Cristallografia, Consiglio Nazionale delle Ricerche, I-95126, Catania, Italy. Electronic address: danilo.milardi@cnr.it.
⁵ PhotoChemLab, Department of Drug and Health Sciences, University of Catania, I-95125, Catania, Italy. Electronic address: ssortino@unict.it.
⁶ Department of Chemical Sciences, University of Catania, I-95125, Catania, Italy. Electronic address: grassog@unict.it.

PMID: 35863477
DOI: 10.1016/j.abb.2022.109354

Abstract

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.

Keywords: Aggregation; Amylin; Amyloid; Fluorescence; Insulin; Ubiquitin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloid
Amyloid beta-Peptides*
Amyloidogenic Proteins*
Dipyridamole
Islet Amyloid Polypeptide

Substances

Amyloid
Amyloid beta-Peptides
Amyloidogenic Proteins
Islet Amyloid Polypeptide
Dipyridamole