ArticleJournal of neuroinflammation2016
Fingolimod promotes peripheral nerve regeneration via modulation of lysophospholipid signaling.
Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Lysophosphatidic acid mediates skeletal muscle fibrosis in denervation via activation of YAP/TAZ.JCI insight · 2026Article
- Targeted lipidomics dataset of central nervous system and plasma from mice with experimental autoimmune encephalomyelitis.Data in brief · 2025Article
- Unraveling the Role of Autotaxin and Lysophosphatidic Acid in Alzheimer's Disease: From Molecular Mechanisms to Therapeutic Potential.International journal of molecular sciences · 2025Review
- Colorectal Cancer: Therapeutic Approaches and Their Complications.Biomedicines · 2025Review
- Effects of Sphingosine-1-Phosphate on the Facilitation of Peripheral Nerve Regeneration.Cureus · 2024Article
- Enhancement of Heme-Oxygenase 1 in the Injured Peripheral Nerve Following Sulforaphane Administration Fosters Regeneration via Proliferation and Maintenance of Repair Schwann Cells.Antioxidants (Basel, Switzerland) · 2024Article
- Focus on LPA signaling: a promising therapeutic target to foster regeneration in immune-mediated neuropathies.Neural regeneration research · 2023Article
- Visualizing Sphingosine-1-Phosphate Receptor 1(S1PCellular and molecular neurobiology · 2023Article
- Molecular Pharmacology and Novel Potential Therapeutic Applications of Fingolimod.Frontiers in pharmacology · 2022Review
- Updates in the Treatment of Chemotherapy-Induced Peripheral Neuropathy.Current treatment options in oncology · 2022Review
- LPAJournal of neuroinflammation · 2021Article
- Aligned Fingolimod-Releasing Electrospun Fibers Increase Dorsal Root Ganglia Neurite Extension and Decrease Schwann Cell Expression of Promyelinating Factors.Frontiers in bioengineering and biotechnology · 2020Article
- Pleotropic Roles of Autotaxin in the Nervous System Present Opportunities for the Development of Novel Therapeutics for Neurological Diseases.Molecular neurobiology · 2020Review
- Recent Developments of Novel Pharmacologic Therapeutics for Prevention of Chemotherapy-Induced Peripheral Neuropathy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Review
- Metformin protects against sevoflurane-induced neuronal apoptosis through the S1P1 and ERK signaling pathways.Experimental and therapeutic medicine · 2019Article
- Targeting lysophospholipid signaling as a therapeutic approach towards improved peripheral nerve regeneration.Neural regeneration research · 2016Article
- Biological Effects of Naturally Occurring Sphingolipids, Uncommon Variants, and Their Analogs.Neuromolecular medicine · 2016Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe lysophospholipids sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) are pleiotropic signaling molecules with a broad range of physiological functions. Targeting the S1P1 receptor on lymphocytes with the immunomodulatory drug fingolimod has proven effective in the treatment of multiple sclerosis. An emerging body of experimental evidence points to additional direct effects on cells of the central and peripheral nervous system. Furthermore, fingolimod has been reported to reduce LPA synthesis via inhibition of the lysophospholipase autotaxin. Here we investigated whether modulation of particular signaling aspects of S1P as well as LPA by fingolimod might propagate peripheral nerve regeneration in vivo and independent of its anti-inflammatory potency.
methodsSciatic nerve crush was performed in wildtype C57BL/6, in immunodeficient Rag1 (-/-) and Foxn1 (-/-) mice. Analyses were based on walking track analysis and electrophysiology, histology, and cAMP formation. Quantification of different LPA species was performed by liquid chromatography coupled to tandem mass spectrometry. Furthermore, functional consequences of autotaxin inhibition by the specific inhibitor PF-8380 and the impact of fingolimod on early cytokine release in the injured sciatic nerve were investigated.
resultsClinical and electrophysiological measures indicated an improvement of nerve regeneration under fingolimod treatment that is partly independent of its anti-inflammatory properties. Fingolimod treatment correlated with a significant elevation of axonal cAMP, a crucial factor for axonal outgrowth. Additionally, fingolimod significantly reduced LPA levels in the injured nerve. PF-8380 treatment correlated with improved myelin thickness. Sciatic nerve cytokine levels were not found to be significantly altered by fingolimod treatment.
conclusionsOur findings provide in vivo evidence for direct effects of fingolimod on cells of the peripheral nervous system that may propagate nerve regeneration via a dual mode of action, differentially affecting axonal outgrowth and myelination by modulating relevant aspects of S1P and LPA signaling.
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