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Briones MRS, Snyder AM, Ferreira RC, et al. A Possible Role for Platelet-Activating Factor Receptor in Amyotrophic Lateral Sclerosis Treatment. Front Neurol. 2018;9:39doi: 10.3389/fneur.2018.00039.
Briones, M. R. S., Snyder, A. M., Ferreira, R. C., Neely, E. B., Connor, J. R., & Broach, J. R. (2018). A Possible Role for Platelet-Activating Factor Receptor in Amyotrophic Lateral Sclerosis Treatment. Frontiers in neurology, 939. https://doi.org/10.3389/fneur.2018.00039
Briones, Marcelo R S, et al. "A Possible Role for Platelet-Activating Factor Receptor in Amyotrophic Lateral Sclerosis Treatment." Frontiers in neurology vol. 9 (2018): 39. doi: https://doi.org/10.3389/fneur.2018.00039
Briones MRS, Snyder AM, Ferreira RC, Neely EB, Connor JR, Broach JR. A Possible Role for Platelet-Activating Factor Receptor in Amyotrophic Lateral Sclerosis Treatment. Front Neurol. 2018 Feb 06;9:39. doi: 10.3389/fneur.2018.00039. eCollection 2018. PMID: 29472887; PMCID: PMC5810282.
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Front Neurol. 2018 Feb 06;9:39. doi: 10.3389/fneur.2018.00039. eCollection 2018.

A Possible Role for Platelet-Activating Factor Receptor in Amyotrophic Lateral Sclerosis Treatment.

Frontiers in neurology

Marcelo R S Briones, Amanda M Snyder, Renata C Ferreira, Elizabeth B Neely, James R Connor, James R Broach

Affiliations

  1. Department of Health Informatics, Escola Paulista de Medicina, UNIFESP, São Paulo, São Paulo, Brazil.
  2. Department of Biochemistry, Penn State College of Medicine, Institute for Personalized Medicine, Hershey, PA, United States.
  3. Department of Neurosurgery, Penn State College of Medicine, Hershey, PA, United States.
  4. Department of Neurology and Neurosurgery, Escola Paulista de Medicina, UNIFESP, São Paulo, São Paulo, Brazil.

PMID: 29472887 PMCID: PMC5810282 DOI: 10.3389/fneur.2018.00039

Abstract

Amyotrophic lateral sclerosis (ALS) is the third most prevalent neurodegenerative disease affecting upper and lower motor neurons. An important pathway that may lead to motor neuron degeneration is neuroinflammation. Cerebrospinal Fluids of ALS patients have increased levels of the inflammatory cytokine IL-18. Because IL-18 is produced by dendritic cells stimulated by the platelet-activating factor (PAF), a major neuroinflammatory mediator, it is expected that PAF is involved in ALS. Here we show pilot experimental data on amplification of PAF receptor (PAFR) mRNA by RT-PCR. PAFR is overexpressed, as compared to age matched controls, in the spinal cords of transgenic ALS SOD1-G93A mice, suggesting PAF mediation. Although anti-inflammatory drugs have been tested for ALS before, no clinical trial has been conducted using PAFR specific inhibitors. Therefore, we hypothesize that administration of PAFR inhibitors, such as Ginkgolide B, PCA 4248 and WEB 2086, have potential to function as a novel therapy for ALS, particularly in SOD1 familial ALS forms. Because currently there are only two approved drugs with modest effectiveness for ALS therapy, a search for novel drugs and targets is essential.

Keywords: amyotrophic lateral sclerosis; anti-inflammatory; cytokines; neuroinflammation; platelet-activating factor

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