ArticleMolecular biology of the cell2011
Tissue-nonspecific alkaline phosphatase promotes axonal growth of hippocampal neurons.
Article in Molecular biology of the cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- Genetic variants in the folate metabolic pathway genes predict cutaneous melanoma-specific survival.The British journal of dermatology · 2020Pooled it
- Hypophosphatasia-pathophysiological understanding, preclinical data looking beyond the skeleton, and upcoming treatments.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Review
- Neuronal alkaline phosphatase promotes the spread of Tau-induced pathology, and its blockade prevents neurodegeneration and memory loss.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Deficiency of Tissue Nonspecific Alkaline Phosphatase Dysregulates Microglial Morphology and Function in a Mouse Model of Infantile Hypophosphatasia.Journal of neurochemistry · 2026Article
- ST3 beta-galactoside alpha-2,3-sialyltransferase 4 (St3gal4) deficiency reveals correlations among alkaline phosphatase activity, metabolic parameters, and fear-related behavior in mice.Metabolic brain disease · 2025Article
- Review
- Blockade of brain alkaline phosphatase efficiently reduces amyloid-β plaque burden and associated cognitive impairment.Alzheimer's research & therapy · 2024Article
- DUSP1/MKP-1 represents another piece in the P2X7R intracellular signaling puzzle in cerebellar cells: our last journey with Mª Teresa along the purinergic pathways of Eden.Purinergic signalling · 2024Article
- Diadenosine pentaphosphate regulates dendrite growth and number in cultured hippocampal neurons.Purinergic signalling · 2024Article
- Musculoskeletal and neurocognitive clinical significance of adult hypophosphatasia.Osteoporosis and sarcopenia · 2023Review
- TNAP and P2X7R: New Plasma Biomarkers for Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Dual Role of the P2X7 Receptor in Dendritic Outgrowth during Physiological and Pathological Brain Development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Serum alkaline phosphatase was independently associated with depression in patients with cerebrovascular disease.Frontiers in psychiatry · 2023Article
- Azomethine-clubbed thiazoles as human tissue non-specific alkaline phosphatase (h-TNAP) and intestinal alkaline phosphatase (h-IAP) Inhibitors: kinetics and molecular docking studies.Molecular diversity · 2022Article
- TNAP as a therapeutic target for cardiovascular calcification: a discussion of its pleiotropic functions in the body.Cardiovascular research · 2022Review
- Studying the Role of P2X7 Receptor in Axonal Growth Using In Utero Electroporation Technique.Methods in molecular biology (Clifton, N.J.) · 2022Article
- How Are Adenosine and Adenosine ABiomedicines · 2021Review
- Salient brain entities labelled in P2rx7-EGFP reporter mouse embryos include the septum, roof plate glial specializations and circumventricular ependymal organs.Brain structure & function · 2021Article
- TNAP as a New Player in Chronic Inflammatory Conditions and Metabolism.International journal of molecular sciences · 2021Review
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Axonal growth is essential for establishing neuronal circuits during brain development and for regenerative processes in the adult brain. Unfortunately, the extracellular signals controlling axonal growth are poorly understood. Here we report that a reduction in extracellular ATP levels by tissue-nonspecific alkaline phosphatase (TNAP) is essential for the development of neuritic processes by cultured hippocampal neurons. Selective blockade of TNAP activity with levamisole or specific TNAP knockdown with short hairpin RNA interference inhibited the growth and branching of principal axons, whereas addition of alkaline phosphatase (ALP) promoted axonal growth. Neither activation nor inhibition of adenosine receptors affected the axonal growth, excluding the contribution of extracellular adenosine as a potential hydrolysis product of extracellular ATP to the TNAP-mediated effects. TNAP was colocalized at axonal growth cones with ionotropic ATP receptors (P2X₇ receptor), whose activation inhibited axonal growth. Additional analyses suggested a close functional interrelation of TNAP and P2X₇ receptors whereby TNAP prevents P2X₇ receptor activation by hydrolyzing ATP in the immediate environment of the receptor. Furthermore inhibition of P2X₇ receptor reduced TNAP expression, whereas addition of ALP enhanced P2X₇ receptor expression. Our results demonstrate that TNAP, regulating both ligand availability and protein expression of P2X₇ receptor, is essential for axonal development.
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Registered trials
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