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Article type: Research Article
Authors: McClure, Richarda | Redha, Reyd | Vinson, Paiged; e | Pham, Wellingtona; b; c; f; g; h; i; *
Affiliations: [a] Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA | [b] Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA | [c] Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA | [d] Vanderbilt High-Throughput Screening Facility, Nashville, TN, USA | [e] Department of Biochemistry, Vanderbilt University, Nashville, TN, USA | [f] Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA | [g] Vanderbilt Ingram Cancer Center, Nashville, TN, USA | [h] Vanderbilt Institute of Chemical Biology, Nashville, TN, USA | [i] Vanderbilt Institute of Nanoscale Science and Engineering, Nashville, TN, USA
Correspondence: [*] Correspondence to: Wellington Pham, Department of Radiology and Radiological Sciences, Vanderbilt University School of Medicine, Institute of Imaging Science, 1161, 21st Avenue South, Nashville, TN 37232-2310, USA. Tel.: +1 615 936 7621; E-mail: [email protected].
Abstract: A robust fluorescent readout assay using topologically-sensitive dyes improves the screening of novel amyloid-binding molecules. One of the key components that make this assay more realistic is the use of endogenous amyloid obtained from 5XFAD mouse brains. The assay conditions were optimized for high throughput screening operation with Z-prime values >0.6. Using a combination of library of 3,500 compounds including known drugs, natural-derived molecules and random organic molecules, 8 unique molecules were identified as potential amyloid-binding agents.
Keywords: Alzheimer’s disease, amyloid, high throughput screening
DOI: 10.3233/JAD-190316
Journal: Journal of Alzheimer's Disease, vol. 70, no. 1, pp. 187-197, 2019
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