ArticleActa neuropathologica communications2018
5-HIAA induces neprilysin to ameliorate pathophysiology and symptoms in a mouse model for Alzheimer's disease.
Article in Acta neuropathologica communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- Exploratory Screening and Replication of Urinary Biomarkers of Fruit and Vegetable Intake in Free-living European Children and Adolescents Using Untargeted Metabolomics.The Journal of nutrition · 2026Article
- 4-HIAA Blocks Methamphetamine-Induced Conditioned Place Preference in Mice Through Modulation of the 5-HT Pathway in the Nucleus Accumbens.Addiction biology · 2025Article
- Celastrol attenuates Alzheimer's disease-mediated learning and memory impairment by inhibiting endoplasmic reticulum stress-induced inflammation and oxidative stress.Archives of medical science : AMS · 2025Article
- The role of the tryptophan metabolites in gut microbiota-brain axis and potential treatments: a focus on ischemic stroke.Frontiers in pharmacology · 2025Review
- Therapeutic Efficacy and Promise of Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles in Aging and Age-Related Disorders.International journal of molecular sciences · 2024Review
- The Kynurenine Pathway, Aryl Hydrocarbon Receptor, and Alzheimer's Disease.Brain sciences · 2024Review
- Association between small intestine bacterial overgrowth and psychiatric disorders.Frontiers in endocrinology · 2024Review
- Advances in Amyloid-β Clearance in the Brain and Periphery: Implications for Neurodegenerative Diseases.Experimental neurobiology · 2023Review
- Microglial targeted therapy relieves cognitive impairment caused byExploration (Beijing, China) · 2023Article
- Kynurenine Metabolism and Alzheimer's Disease: The Potential Targets and Approaches.Neurochemical research · 2022Review
- Host-microbiota interactions: The aryl hydrocarbon receptor in the acute and chronic phases of cerebral ischemia.Frontiers in immunology · 2022Review
- Based on molecular structures: Amyloid-β generation, clearance, toxicity and therapeutic strategies.Frontiers in molecular neuroscience · 2022Review
- Article
- Synthesis and Biological Evaluation of Hydroxylated Monocarbonyl Curcumin Derivatives as Potential Inducers of Neprilysin Activity.Biomedicines · 2021Article
- Extracellular Vesicles Released from Neprilysin Gene-Modified Human Umbilical Cord-Derived Mesenchymal Stem Cell Enhance Therapeutic Effects in an Alzheimer's Disease Animal Model.Stem cells international · 2021Article
- Activating AhR alleviates cognitive deficits of Alzheimer's disease model mice by upregulating endogenous Aβ catabolic enzyme Neprilysin.Theranostics · 2021Article
- Targeting Neprilysin (NEP) pathways: A potential new hope to defeat COVID-19 ghost.Biochemical pharmacology · 2020Review
- Expression of Neprilysin in Skeletal Muscle by Ultrasound-Mediated Gene Transfer (Sonoporation) Reduces Amyloid Burden for AD.Molecular therapy. Methods & clinical development · 2020Article
- Target Enzymes Considered for the Treatment of Alzheimer's Disease and Parkinson's Disease.BioMed research international · 2020Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Serotoninergic activation which decreases brain Aβ peptides is considered beneficial in mouse models for Alzheimer's disease (AD), but the mechanisms involved remain unclear. Because growing evidence suggested that the stimulation of proteases digesting Aβ, especially the endopeptidase neprilysin (NEP) may be effective for AD therapy/prevention, we explored the involvement of serotonin precursors and derivatives in NEP regulation. We found that 5-hydroxyindolacetic acid (5-HIAA), the final metabolite of serotonin, considered until now as a dead-end and inactive product of serotonin catabolism, significantly reduces brain Aβ in the transgenic APPSWE mouse model for AD-related Aβ pathology and in the phosphoramidon-induced cerebral NEP inhibition mouse model. 5-HIAA treatment improves memory performance in APPSWE mice. Furthermore, 5-HIAA and its precursors increase NEP level in vivo and in neuroblastoma cells. Inhibition of ERK 1/2 cascade by 5-HIAA or SCH772984 enhanced NEP levels, suggesting MAP-kinase pathway involvement in 5-HIAA-induced regulation of NEP expression. Our results provide the first demonstration that 5-HIAA is an active serotonin metabolite that increases brain Aβ degradation/clearance and improves symptoms in the APPSWE mouse model for AD.
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