Bicine promotes rapid formation of β-sheet-rich amyloid-β fibrils

Hye Yun Kim; HeeYang Lee; Jong Kook Lee; Hyunjin Vincent Kim; Key-Sun Kim; YoungSoo Kim

doi:10.1371/journal.pone.0240608

Bicine promotes rapid formation of β-sheet-rich amyloid-β fibrils

PLoS One. 2020 Oct 13;15(10):e0240608. doi: 10.1371/journal.pone.0240608. eCollection 2020.

Authors

Hye Yun Kim^{1

2}, HeeYang Lee^{1

2

3}, Jong Kook Lee⁴, Hyunjin Vincent Kim⁴, Key-Sun Kim⁴, YoungSoo Kim^{1

2

3}

Affiliations

¹ Department of Pharmacy, Yonsei University, Incheon, Republic of Korea.
² Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea.
³ Integrated Science and Engineering Division, Yonsei University, Incheon, Republic of Korea.
⁴ Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea.

Abstract

Fibrillar aggregates of amyloid-β (Aβ) are the main component of plaques lining the cerebrovasculature in cerebral amyloid angiopathy. As the predominant Aβ isoform in vascular deposits, Aβ40 is a valuable target in cerebral amyloid angiopathy research. However, the slow process of Aβ40 aggregation in vitro is a bottleneck in the search for Aβ-targeting molecules. In this study, we sought a method to accelerate the aggregation of Aβ40 in vitro, to improve experimental screening procedures. We evaluated the aggregating ability of bicine, a biological buffer, using various in vitro methods. Our data suggest that bicine promotes the aggregation of Aβ40 with high speed and reproducibility, yielding a mixture of aggregates with significant β-sheet-rich fibril formation and toxicity.

Publication types

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

MeSH terms

Amyloid beta-Peptides / metabolism*
Amyloid beta-Peptides / toxicity
Animals
Cell Line
Cell Survival
Cerebral Amyloid Angiopathy / pathology*
Glycine / analogs & derivatives*
Glycine / pharmacology
Humans
Mice
Neurons
Peptide Fragments / metabolism*
Peptide Fragments / toxicity
Protein Aggregates / drug effects*
Protein Conformation, beta-Strand / drug effects

Substances

Amyloid beta-Peptides
Peptide Fragments
Protein Aggregates
amyloid beta-protein (1-40)
N,N-bis(2-hydroxyethyl)glycine
Glycine

Grants and funding

This work was supported by National Research Foundation of Korea (NRF-2018R1A6A1A03023718 and NRF-2018R1D1A1B07048857), and POSCO Science Fellowship of POSCO TJ Park Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.