Epidermal growth factor receptor is a preferred target for treating Amyloid-β–induced memory loss
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Current understanding of amyloid-β (Aβ) metabolism and toxicity provides an extensive list of potential targets for developing drugs for treating Alzheimer’s disease. We took two independent approaches, including synaptic-plasticity–based analysis and behavioral screening of synthetic compounds, for identifying single compounds that are capable of rescuing the Aβ-induced memory loss in both transgenic fruit fly and transgenic mouse models. Two clinically available drugs and three synthetic compounds not only showed positive effects in behavioral tests but also antagonized the Aβ oligomers-induced activation of the epidermal growth factor receptor (EGFR). Such surprising converging outcomes from two parallel approaches lead us to conclude that EGFR is a preferred target for treating Aβ-induced memory loss.
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NanoString data confirmed increased astrocyte expression of EGFR, which has been proposed as a potential amyloid beta receptor and a regulator of astrocytes in multiple sclerosis.
“as well as increased astrocyte expression of EGFR, which has been proposed as a potential receptor for Aβ37, and a regulator of astrocytes in multiple sclerosis38.”
From Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease (2020) · cites this paper as [37]
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- Authors
- Wang, L., Chiang, H.-C., Wu, W., Liang, B., Xie, Z., Yao, X., Ma, W., Du, S., & Zhong, Y.
- Affiliations
- Tsinghua University (CN)
- Cold Spring Harbor Laboratory (US)
- Tsinghua Shenzhen International Graduate School (CN)
- Hainan Normal University (CN)
- JoeKai Biotech, LLC, Beijing 100084, China; and
- Division of Life Science and Health, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China;
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-09-27
- Volume
- 109
- Issue
- 41
- Pages
- 16743-16748
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3478595
- OpenAlex
- W2091619946
- Cited by
- 190
- References
- 45
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 21 · 2023: 25 · 2022: 14 · 2021: 18 · 2020: 13 · 2019: 11 · 2018: 8 · 2017: 14 · 2016: 8 · 2015: 11 · 2014: 14 · 2013: 6 · 2012: 2
- FWCI
- 7.07
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- epidermal growth factor receptor, amyloid-beta, Alzheimer's disease, memory loss, amyloid-beta oligomers, synaptic plasticity, behavioral screening, synthetic compounds, drug repurposing, transgenic mouse model
- MeSH terms
- Erlotinib Hydrochloride, Gefitinib, Animals, Chlorocebus aethiops, Drosophila, Drug Evaluation, Preclinical, Humans, Memantine, Memory, Memory Disorders, Mice, Transgenic, Peptide Fragments, Quinazolines, Blotting, Western, Molecular Structure, Amyloid beta-Peptides, Maze Learning, COS Cells, Drosophila Proteins, Animals, Genetically Modified, Protein Kinase Inhibitors, Mice, ErbB Receptors
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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