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Cited by 27Alzheimer's disease research and treatmentsMolecular Sensors and Ion DetectionDementia and Cognitive Impairment Research

A chemical screening approach reveals that indole fluorescence is quenched by pre-fibrillar but not fibrillar amyloid-β

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Reinke, Ashley A., Seh, Han Yiau, Gestwicki, Jason E.·2009·Bioorganic & Medicinal Chemistry Letters
DOI 10.1016/j.bmcl.2009.07.082PMC PMC2730169
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Abstract

Aggregated amyloid-beta (Abeta) peptide is implicated in the pathology of Alzheimer's disease. In vitro and in vivo, these aggregates are found in a variety of morphologies, including globular oligomers and linear fibrils, which possess distinct biological activities. However, known chemical probes, including the dyes thioflavin T and Congo Red, appear to lack selectivity for specific amyloid structures. To identify molecules that might differentiate between these architectures, we employed a fluorescence-based interaction assay to screen a collection of 68 known Abeta ligands against pre-formed oligomers and fibrils. In these studies, we found that the fluorescence of five indole-based compounds was selectively quenched ( approximately 15%) in the presence of oligomers, but remained unchanged after addition of fibrils. These results suggest that indoles might be complementary to existing chemical probes for studying amyloid formation in vitro.

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  • The lack of change in L2 emission in presence of Aβ fibrils is likely not due to lack of L2 binding to Aβ fibrils, but merely a failure of Aβ to impact the fluorescence of L2.

    “This behavior is likely not due to the lack of L2 binding to Aβ fibrils, but is merely a failure of Aβ to impact the fluorescence of L2.86”

    From Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ<sub>42</sub>Peptide (2012) · cites this paper as [86]

    In Results, under “Fluorescence screen for Aβ conformation-specific small molecules” (page unavailable), the paper says unchanged fluorescence should not be interpreted as failure to bind. It does not study L2 or establish that L2 binds Aβ fibrils, so it supports the citing sentence’s interpretive caution but not its L2-specific explanation. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Authors
Reinke, A. A., Seh, H. Y., & Gestwicki, J. E.
Affiliations
University of Michigan (US)
Corresponding author
Gestwicki, Jason E.
ORCID
Gestwicki, Jason E.
Venue
Bioorganic & Medicinal Chemistry Letters
Publisher
Elsevier BV
Published
2009-09
Volume
19
Issue
17
Pages
4952-4957
ISSN
0960-894X (ISSN-L)
DOI
10.1016/j.bmcl.2009.07.082
PMC
PMC2730169
OpenAlex
W2018824572
Cited by
26
References
41
Citations by year
2025: 2 · 2021: 1 · 2020: 4 · 2018: 1 · 2015: 3 · 2013: 1 · 2012: 6
FWCI
2.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Bioorganic & Medicinal Chemistry Letters (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (Z01AG000114, AG 000114, T32AG000114)
  • National Institute of Neurological Disorders and Stroke (R01NS059690)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Physical Sciences › Chemistry › Spectroscopy › Molecular Sensors and Ion Detection
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
amyloid-beta, fibrils, indole derivatives, fluorescence quenching, chemical probes, Alzheimer's disease, ligand screening, thioflavin T, Congo red
MeSH terms
Congo Red, Coloring Agents, Fluorescent Dyes, Indoles, Spectrometry, Fluorescence, Thiazoles, Amyloid beta-Peptides, Benzothiazoles

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