ArticleProceedings of the National Academy of Sciences of the United States of America2017
ErbB2 regulates autophagic flux to modulate the proteostasis of APP-CTFs in Alzheimer's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 2 syntheses or guidelines pooled it, 88 citations in OpenAlex.
- Gene co-expression changes underlying the functional connectomic alterations in Alzheimer's disease.BMC medical genomics · 2022Pooled it
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- Chronic oral administration of ibrutinib prevents long-term memory deficits and reduces AD pathology and neuroinflammatory responses in a mouse model of AD.Molecular brain · 2025Article
- EGF receptor in organ development, tissue homeostasis and regeneration.Journal of biomedical science · 2025Review
- Neuroprotective Potential of Aminonaphthoquinone Derivatives Against Amyloid Beta-Induced Neuronal Cell Death Through Modulation of SIRT1 and BACE1.Neurochemical research · 2024Article
- Dementia incidence varied by anticancer drugs and molecular targeted therapy in a population-based cohort study.Scientific reports · 2024Article
- International consensus guidelines for the definition, detection, and interpretation of autophagy-dependent ferroptosis.Autophagy · 2024Review
- Research Progress of Mitophagy in Alzheimer's Disease.Current Alzheimer research · 2024Review
- REDOX Balance in Oligodendrocytes Is Important for Zebrafish Visual System Regeneration.Antioxidants (Basel, Switzerland) · 2023Article
- Single-cell-led drug repurposing for Alzheimer's disease.Scientific reports · 2023Article
- Identification of highly reliable risk genes for Alzheimer's disease through joint-tissue integrative analysis.Frontiers in aging neuroscience · 2023Article
- EGFR is a potential dual molecular target for cancer and Alzheimer's disease.Frontiers in pharmacology · 2023Review
- Integrating network pharmacology, UPLC-Q-TOF-MS and molecular docking to investigate the effect and mechanism of Chuanxiong Renshen decoction against Alzheimer's disease.Chinese medicine · 2022Article
- Modulating autophagy and mitophagy as a promising therapeutic approach in neurodegenerative disorders.Life sciences · 2022Review
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- Impaired autophagy in amyloid-beta pathology: A traditional review of recent Alzheimer's research.Journal of biomedical research · 2022Article
- Identification of risk genes for Alzheimer's disease by gene embedding.Cell genomics · 2022Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
Proteolytic processing of amyloid precursor protein (APP) C-terminal fragments (CTFs) by γ-secretase underlies the pathogenesis of Alzheimer's disease (AD). An RNA interference screen using APP-CTF [99-residue CTF (C99)]- and Notch-specific γ-secretase interaction assays identified a unique ErbB2-centered signaling network that was predicted to preferentially govern the proteostasis of APP-C99. Consistently, significantly elevated levels of ErbB2 were confirmed in the hippocampus of human AD brains. We then found that ErbB2 effectively suppressed autophagic flux by physically dissociating Beclin-1 from the Vps34-Vps15 complex independent of its kinase activity. Down-regulation of ErbB2 by CL-387,785 decreased the levels of C99 and secreted amyloid-β in cellular, zebrafish, and mouse models of AD, through the activation of autophagy. Oral administration of an ErbB2-targeted CL-387,785 for 3 wk significantly improves the cognitive functions of APP/presenilin-1 (PS1) transgenic mice. This work unveils a noncanonical function of ErbB2 in modulating autophagy and establishes ErbB2 as a therapeutic target for AD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.