ArticleThe EMBO journal2015
The stress response neuropeptide CRF increases amyloid-β production by regulating γ-secretase activity.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
27 citing papers in PubMed, 55 citations in OpenAlex.
- A structural overview of G-protein-coupled receptors in neurological disorders.Acta pharmacologica Sinica · 2026Review
- Corticotropin-releasing factor (CRF) in brain aging: from mitochondrial dysfunction to inflammaging.Frontiers in aging neuroscience · 2026Review
- Elevated serum cortisol associated with early-detected increase of brain amyloid deposition in Alzheimer's disease imaging biomarkers among menopausal women: The Framingham Heart Study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Navigating the metabolic maze: anomalies in fatty acid and cholesterol processes in Alzheimer's astrocytes.Alzheimer's research & therapy · 2024Review
- Converged avenues: depression and Alzheimer's disease- shared pathophysiology and novel therapeutics.Molecular biology reports · 2024Review
- Circadian dysfunction and Alzheimer's disease - An updated review.Aging medicine (Milton (N.S.W)) · 2023Article
- Neuroimmune connections between corticotropin-releasing hormone and mast cells: novel strategies for the treatment of neurodegenerative diseases.Neural regeneration research · 2021Review
- Decision-Making Support for People With Alzheimer's Disease: A Narrative Review.Frontiers in psychology · 2021Review
- Article
- γ-Secretase modulators exhibit selectivity for modulation of APP cleavage but inverse γ-secretase modulators do not.Alzheimer's research & therapy · 2020Article
- The Locus Coeruleus- Norepinephrine System in Stress and Arousal: Unraveling Historical, Current, and Future Perspectives.Frontiers in psychiatry · 2020Review
- An anti-CRF antibody suppresses the HPA axis and reverses stress-induced phenotypes.The Journal of experimental medicine · 2019Article
- Corticotropin releasing factor-binding protein (CRF-BP) as a potential new therapeutic target in Alzheimer's disease and stress disorders.Translational psychiatry · 2019Review
- Sleep and circadian rhythm disruption and stress intersect in Alzheimer's disease.Neurobiology of stress · 2019Review
- Depression and Sleep.International journal of molecular sciences · 2019Review
- Sexual dimorphism in predisposition to Alzheimer's disease.Neurobiology of aging · 2018Review
- A preclinical perspective on the enhanced vulnerability to Alzheimer's disease after early-life stress.Neurobiology of stress · 2018Review
- Sex differences in chronic stress responses and Alzheimer's disease.Neurobiology of stress · 2018Review
- Membrane-Associated Effects of Glucocorticoid on BACE1 Upregulation and Aβ Generation: Involvement of Lipid Raft-Mediated CREB Activation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Corticotropin-releasing factor overexpression gives rise to sex differences in Alzheimer's disease-related signaling.Molecular psychiatry · 2017Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
The biological underpinnings linking stress to Alzheimer's disease (AD) risk are poorly understood. We investigated how corticotrophin releasing factor (CRF), a critical stress response mediator, influences amyloid-β (Aβ) production. In cells, CRF treatment increases Aβ production and triggers CRF receptor 1 (CRFR1) and γ-secretase internalization. Co-immunoprecipitation studies establish that γ-secretase associates with CRFR1; this is mediated by β-arrestin binding motifs. Additionally, CRFR1 and γ-secretase co-localize in lipid raft fractions, with increased γ-secretase accumulation upon CRF treatment. CRF treatment also increases γ-secretase activity in vitro, revealing a second, receptor-independent mechanism of action. CRF is the first endogenous neuropeptide that can be shown to directly modulate γ-secretase activity. Unexpectedly, CRFR1 antagonists also increased Aβ. These data collectively link CRF to increased Aβ through γ-secretase and provide mechanistic insight into how stress may increase AD risk. They also suggest that direct targeting of CRF might be necessary to effectively modulate this pathway for therapeutic benefit in AD, as CRFR1 antagonists increase Aβ and in some cases preferentially increase Aβ42 via complex effects on γ-secretase.
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Registered trials
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 OpenQuestion graph.