Real-Time BODIPY-Binding Assay To Screen Inhibitors of the Early Oligomerization Process of A beta 1-42 Peptide

Tonali NM, Dodero VI, Kaffy J, Hericks L, Ongeri S, Sewald N (2020)
CHEMBIOCHEM: cbic.201900652.

Zeitschriftenaufsatz | E-Veröff. vor dem Druck | Englisch
 
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Abstract / Bemerkung
Misfolding and aggregation of amyloid beta 1-42 peptide (A beta 1-42) play a central role in the pathogenesis of Alzheimer's disease (AD). Targeting the highly cytotoxic oligomeric species formed during the early stages of the aggregation process represents a promising therapeutic strategy to reduce the toxicity associated with A beta 1-42. Currently, the thioflavin T (ThT) assay is the only established spectrofluorometric method to screen aggregation inhibitors. The success of the ThT assay is that it can detect A beta 1-42 aggregates with high beta-sheet content, such as protofibrils or fibrils, which appear in the late aggregation steps. Unfortunately, by using the ThT assay, the detection of inhibitors of early soluble oligomers that present a low beta-sheet character is challenging. Herein, a new, facile, and robust boron-dipyrromethene (BODIPY) real-time assay suitable for 96-well plate format, which allows screening of compounds as selective inhibitors of the formation of A beta 1-42 oligomers, is reported. These inhibitors decrease the cellular toxicity of A beta 1-42, although they fail in the ThT assay. The findings have been confirmed and validated by structural analysis and cell viability assays under comparable experimental conditions. It is demonstrated that the BODIPY assay is a convenient method to screen and discover new candidate compounds that slow down or stop the pathological early oligomerization process and are active in the cellular assay. Therefore, it is a suitable complementary screening method of the current ThT assay.
Stichworte
Alzheimer's disease; amyloid beta-peptides; fluorescence; inhibitors; oligomerization
Erscheinungsjahr
2020
Zeitschriftentitel
CHEMBIOCHEM
Art.-Nr.
cbic.201900652
ISSN
1439-4227
eISSN
1439-7633
Page URI
https://pub.uni-bielefeld.de/record/2940090

Zitieren

Tonali NM, Dodero VI, Kaffy J, Hericks L, Ongeri S, Sewald N. Real-Time BODIPY-Binding Assay To Screen Inhibitors of the Early Oligomerization Process of A beta 1-42 Peptide. CHEMBIOCHEM. 2020: cbic.201900652.
Tonali, N. M., Dodero, V. I., Kaffy, J., Hericks, L., Ongeri, S., & Sewald, N. (2020). Real-Time BODIPY-Binding Assay To Screen Inhibitors of the Early Oligomerization Process of A beta 1-42 Peptide. CHEMBIOCHEM, cbic.201900652. doi:10.1002/cbic.201900652
Tonali, N. M., Dodero, V. I., Kaffy, J., Hericks, L., Ongeri, S., and Sewald, N. (2020). Real-Time BODIPY-Binding Assay To Screen Inhibitors of the Early Oligomerization Process of A beta 1-42 Peptide. CHEMBIOCHEM:cbic.201900652.
Tonali, N.M., et al., 2020. Real-Time BODIPY-Binding Assay To Screen Inhibitors of the Early Oligomerization Process of A beta 1-42 Peptide. CHEMBIOCHEM, : cbic.201900652.
N.M. Tonali, et al., “Real-Time BODIPY-Binding Assay To Screen Inhibitors of the Early Oligomerization Process of A beta 1-42 Peptide”, CHEMBIOCHEM, 2020, : cbic.201900652.
Tonali, N.M., Dodero, V.I., Kaffy, J., Hericks, L., Ongeri, S., Sewald, N.: Real-Time BODIPY-Binding Assay To Screen Inhibitors of the Early Oligomerization Process of A beta 1-42 Peptide. CHEMBIOCHEM. : cbic.201900652 (2020).
Tonali, Nicolo Michele, Dodero, Veronica Isabel, Kaffy, Julia, Hericks, Loreen, Ongeri, Sandrine, and Sewald, Norbert. “Real-Time BODIPY-Binding Assay To Screen Inhibitors of the Early Oligomerization Process of A beta 1-42 Peptide”. CHEMBIOCHEM (2020): cbic.201900652.

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