ArticleMolecular neurobiology2018
Inhibition of γ-Secretase Leads to an Increase in Presenilin-1.
Article in Molecular neurobiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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
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Who cites it
11 citing papers in PubMed, 24 citations in OpenAlex.
- Rotenone Induces a Neuropathological Phenotype in Cholinergic-like Neurons Resembling Parkinson's Disease Dementia (PDD).Neurotoxicity research · 2024Article
- Secretase promotes AD progression: simultaneously cleave Notch and APP.Frontiers in aging neuroscience · 2024Review
- The epilepsy-associated protein PCDH19 undergoes NMDA receptor-dependent proteolytic cleavage and regulates the expression of immediate-early genes.Cell reports · 2022Article
- Role of Presenilin-1 in Aggressive Human Melanoma.International journal of molecular sciences · 2022Article
- Presenilin Is Essential for ApoE Secretion, a Novel Role of Presenilin Involved in Alzheimer's Disease Pathogenesis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Understanding the Modulatory Effects of Cannabidiol on Alzheimer's Disease.Brain sciences · 2021Review
- Article
- Side-by-side comparison of Notch- and C83 binding to γ-secretase in a complete membrane model at physiological temperature.RSC advances · 2020Article
- Amyloid precursor protein glycosylation is altered in the brain of patients with Alzheimer's disease.Alzheimer's research & therapy · 2020Article
- Characterization of Cerebrospinal Fluid BACE1 Species.Molecular neurobiology · 2019Article
- Recent Progress in the Pharmacotherapy of Alzheimer's Disease.Drugs & aging · 2017Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
γ-Secretase inhibitors (GSIs) are potential therapeutic agents for Alzheimer's disease (AD); however, trials have proven disappointing. We addressed the possibility that γ-secretase inhibition can provoke a rebound effect, elevating the levels of the catalytic γ-secretase subunit, presenilin-1 (PS1). Acute treatment of SH-SY5Y cells with the GSI LY-374973 (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester, DAPT) augments PS1, in parallel with increases in other γ-secretase subunits nicastrin, presenilin enhancer 2, and anterior pharynx-defective 1, yet with no increase in messenger RNA expression. Over-expression of the C-terminal fragment (CTF) of APP, C99, also triggered an increase in PS1. Similar increases in PS1 were evident in primary neurons treated repeatedly (4 days) with DAPT or with the GSI BMS-708163 (avagacestat). Likewise, rats examined after 21 days administered with avagacestat (40 mg/kg/day) had more brain PS1. Sustained γ-secretase inhibition did not exert a long-term effect on PS1 activity, evident through the decrease in CTFs of APP and ApoER2. Prolonged avagacestat treatment of rats produced a subtle impairment in anxiety-like behavior. The rebound increase in PS1 in response to GSIs must be taken into consideration for future drug development.
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Registered trials
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