ArticlePloS one2014
Regulation of amyloid precursor protein processing by serotonin signaling.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- Glial Cells in Behavioral and Psychological Symptoms of Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Immune-proteo-metabolomic changes link to Aβ and tau pathology in Alzheimer disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Neuroprotective Effects of Hesperidin and CK2 Inhibitor DRB on AβMolecular neurobiology · 2025Article
- The interaction between neurotransmitter receptor activity and amyloid-β pathology in Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Review
- Beta-amyloid influences the content and trafficking of beta-amyloid precursor protein via Na,K-ATPase-Src kinase positive feedback loop.Frontiers in pharmacology · 2025Article
- Intestinal Flora Affect Alzheimer's Disease by Regulating Endogenous Hormones.Neurochemical research · 2022Review
- Metabolomics as a Crucial Tool to Develop New Therapeutic Strategies for Neurodegenerative Diseases.Metabolites · 2022Review
- Article
- Protein Kinase CK2 and Its Potential Role as a Therapeutic Target in Huntington's Disease.Biomedicines · 2022Review
- Protein kinase CK2: a potential therapeutic target for diverse human diseases.Signal transduction and targeted therapy · 2021Review
- Metabolic phenotyping reveals a reduction in the bioavailability of serotonin and kynurenine pathway metabolites in both the urine and serum of individuals living with Alzheimer's disease.Alzheimer's research & therapy · 2021Article
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Src Family Kinases in the Central Nervous System: Their Emerging Role in Pathophysiology of Migraine and Neuropathic Pain.Current neuropharmacology · 2021Article
- Learning to encode cellular responses to systematic perturbations with deep generative models.NPJ systems biology and applications · 2020Article
- Gene expression of serotonergic markers in peripheral blood mononuclear cells of patients with late-onset Alzheimer's disease.Heliyon · 2020Article
- Influence of the Mediterranean and Ketogenic Diets on Cognitive Status and Decline: A Narrative Review.Nutrients · 2020Review
- Effect of memantine combined with citalopram on cognition of BPSD and moderate Alzheimer's disease: A clinical trial.Experimental and therapeutic medicine · 2019Article
- The Dynamics of Neurosteroids and Sex-Related Hormones in the Pathogenesis of Alzheimer's Disease.Neuromolecular medicine · 2018Review
- Branched-chain amino acids and Alzheimer's disease: a Mendelian randomization analysis.Scientific reports · 2017Article
- Analyzing the genes related to Alzheimer's disease via a network and pathway-based approach.Alzheimer's research & therapy · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteolytic processing of the amyloid precursor protein (APP) by the β- and γ-secretases releases the amyloid-β peptide (Aβ), which deposits in senile plaques and contributes to the etiology of Alzheimer's disease (AD). The α-secretase cleaves APP in the Aβ peptide sequence to generate soluble APPα (sAPPα). Upregulation of α-secretase activity through the 5-hydroxytryptamine 4 (5-HT4) receptor has been shown to reduce Aβ production, amyloid plaque load and to improve cognitive impairment in transgenic mouse models of AD. Consequently, activation of 5-HT4 receptors following agonist stimulation is considered to be a therapeutic strategy for AD treatment; however, the signaling cascade involved in 5-HT4 receptor-stimulated proteolysis of APP remains to be determined. Here we used chemical and siRNA inhibition to identify the proteins which mediate 5-HT4d receptor-stimulated α-secretase activity in the SH-SY5Y human neuronal cell line. We show that G protein and Src dependent activation of phospholipase C are required for α-secretase activity, while, unexpectedly, adenylyl cyclase and cAMP are not involved. Further elucidation of the signaling pathway indicates that inositol triphosphate phosphorylation and casein kinase 2 activation is also a prerequisite for α-secretase activity. Our findings provide a novel route to explore the treatment of AD through 5-HT4 receptor-induced α-secretase activation.
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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.