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Prominence of Central Sphingosine-1-Phosphate Receptor-1 in Attenuating Aβ-Induced Injury by Fingolimod

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Abstract

FTY720 (fingolimod), the sphingosine-1-phosphate (S1P) analogue, has been experimentally indicated to exert substantial ameliorating effects in animal models of Alzheimer’s disease (AD). The present work aims to answer whether central S1P receptor 1 (S1P1) plays significant role in the impact of fingolimod in AD. To verify the prominence of central FTY720 phosphorylation, DMS (sphingosine kinase inhibitor) was infused intracerebrally in parallel with systemic FTY720 administration to prevent central formation of FTY720-P as the recognized active ligand for S1PRs. The corresponding S1P1 modulation was also investigated using the pharmacological blockage of central S1P1 by W123. Both DMS and W123 were efficiently capable of suppressing FTY720-ameliorating effects in AD animals, either on memory deficit or on COX-II and TNF-α expression. Our data conclude that experimental benefits of FTY720 in the context of AD depend on central S1P1 modulation, as well as on S1P kinase activity in the brain.

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Authors and Affiliations

  1. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Masoumeh Asle-Rousta, Zeynab Kolahdooz & Abolhassan Ahmadiani

  2. Department of Biology, Faculty of Basic and Medical Sciences, Zanjan Branch, Islamic Azad University, Zanjan, Iran

    Masoumeh Asle-Rousta

  3. NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Leila Dargahi

  4. Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Abolhassan Ahmadiani

  5. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Science, Postal code: 1991953381, Tehran, Iran

    Sanaz Nasoohi

Authors
  1. Masoumeh Asle-Rousta
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  2. Zeynab Kolahdooz
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  3. Leila Dargahi
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  4. Abolhassan Ahmadiani
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  5. Sanaz Nasoohi
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Correspondence to Sanaz Nasoohi.

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Asle-Rousta, M., Kolahdooz, Z., Dargahi, L. et al. Prominence of Central Sphingosine-1-Phosphate Receptor-1 in Attenuating Aβ-Induced Injury by Fingolimod. J Mol Neurosci 54, 698–703 (2014). https://doi.org/10.1007/s12031-014-0423-3

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  • DOI: https://doi.org/10.1007/s12031-014-0423-3

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