A possible role for platelet-activating factor receptor in amyotrophic lateral sclerosis treatment

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Article number39
JournalFrontiers in Neurology
Volume9
Issue numberFEB
DOIs
StatePublished - Feb 6 2018

Fingerprint

Amyotrophic Lateral Sclerosis
Platelet Activating Factor
ginkgolide B
Interleukin-18
WEB 2086
Motor Neurons
Therapeutics
Pharmaceutical Preparations
Nerve Degeneration
platelet activating factor receptor
Neurodegenerative Diseases
Dendritic Cells
Cerebrospinal Fluid
Spinal Cord
Anti-Inflammatory Agents
Clinical Trials
Cytokines
Polymerase Chain Reaction
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

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title = "A possible role for platelet-activating factor receptor in amyotrophic lateral sclerosis treatment",
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.",
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A possible role for platelet-activating factor receptor in amyotrophic lateral sclerosis treatment. / Briones, Marcelo R.S.; Snyder, Amanda; Ferreira, Renata C.; Neely, Elizabeth B.; Connor, James; Broach, James.

In: Frontiers in Neurology, Vol. 9, No. FEB, 39, 06.02.2018.

Research output: Contribution to journalArticle

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