Methylene blue inhibits nucleation and elongation of SOD1 amyloid fibrils

Greta Musteikyte; Mantas Ziaunys; Vytautas Smirnovas

doi:10.7717/peerj.9719

Methylene blue inhibits nucleation and elongation of SOD1 amyloid fibrils

PeerJ. 2020 Aug 14:8:e9719. doi: 10.7717/peerj.9719. eCollection 2020.

Authors

Greta Musteikyte^{1

2}, Mantas Ziaunys², Vytautas Smirnovas²

Affiliations

¹ Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
² Life Sciences Center, Institute of Biotechnology, Vilnius University, Vilnius, Lithuania.

Abstract

Protein aggregation into highly-structured amyloid fibrils is linked to several neurodegenerative diseases. Such fibril formation by superoxide dismutase I (SOD1) is considered to be related to amyotrophic lateral sclerosis, a late-onset and fatal disorder. Despite much effort and the discovery of numerous anti-amyloid compounds, no effective cure or treatment is currently available. Methylene blue (MB), a phenothiazine dye, has been shown to modulate the aggregation of multiple amyloidogenic proteins. In this work we show its ability to inhibit both the spontaneous amyloid aggregation of SOD1 as well as elongation of preformed fibrils.

Keywords: Amyloid; Fibril elongation; Inhibition; Methylene blue; Nucleation; Protein aggregation; Protein misfolding; Superoxide dismutase.

Grants and funding

This work was supported by the European Social Fund (project No 09.3.3.-LMT-K-712-03-0059) under grant agreement with the Research Council of Lithuania. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.