ArticleScientific reports2017
A tricyclic antidepressant, amoxapine, reduces amyloid-β generation through multiple serotonin receptor 6-mediated targets.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
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- Systemic Modulators: Potential Mechanism for the 5-HT System to Mediate Exercise Amelioration in Alzheimer's Disease.Aging and disease · 2024Review
- Drug repurposing for neurodegenerative diseases using Zebrafish behavioral profiles.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Antidepressant sertraline increases thioflavin-S and Congo red deposition in APPswe/PSEN1dE9 transgenic mice.Frontiers in pharmacology · 2023Article
- Understanding How Physical Exercise Improves Alzheimer's Disease: Cholinergic and Monoaminergic Systems.Frontiers in aging neuroscience · 2022Review
- Antidepressants in Alzheimer's Disease: A Focus on the Role of Mirtazapine.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Constitutive Activity of Serotonin Receptor 6 Regulates Human Cerebral Organoids Formation and Depression-like Behaviors.Stem cell reports · 2021Article
- Constitutive activity of a G protein-coupled receptor, DRD1, contributes to human cerebral organoid formation.Stem cells (Dayton, Ohio) · 2020Article
- Article
- Effects of the Novel IDO Inhibitor DWG-1036 on the Behavior of Male and Female 3xTg-AD Mice.Frontiers in pharmacology · 2019Article
- Serotonin, β-amyloid, and cognition in Parkinson disease.Annals of neurology · 2018Article
- Interactions between stress and physical activity on Alzheimer's disease pathology.Neurobiology of stress · 2018Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is a major and devastating neurodegenerative disease, and the amyloid-β (Aβ) hypothesis is still the central theory for AD pathogenesis. Meanwhile, another major mental illness, depression, is one of the risk factors for AD. From a high-throughput screening (HTS), amoxapine, a typical secondary amine tricyclic antidepressant (TCA), was identified to reduce Aβ production. A follow-up investigation on antidepressants showed that most of the TCAs harbour similar activity. Previous studies have indicated that TCAs improve cognitive function in AD mouse models as well as in preliminary clinical data; however, the underlying mechanism is controversial, and the effect on Aβ is elusive. Thus, we developed a secondary screening to determine the molecular target of amoxapine, and serotonin receptor 6 (HTR6) was identified. Knockdown of HTR6 reduced the amoxapine's effect, while the HTR6 antagonist SB258585 mimicked the activity of amoxapine. Further mechanistic study showed that amoxapine and SB258585 reduced Aβ generation through multiple HTR6-mediated targets, including β-arrestin2 and CDK5. Taken together, our study suggests that amoxapine, though no longer a first-line drug for the treatment of depression, may be beneficial for AD and further structural modification of TCAs may lead to desirable therapeutic agents to treat both AD and depression.
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