A Possible role for Platelet-Activating Factor receptor in Amyotrophic Lateral sclerosis treatment

A Possible role for Platelet-Activating Factor receptor in Amyotrophic Lateral sclerosis treatment

Author Briones, Marcelo R. S. Autor UNIFESP Google Scholar
Snyder, Amanda M. Google Scholar
Ferreira, Renata C. Autor UNIFESP Google Scholar
Neely, Elizabeth B. Google Scholar
Connor, James R. Google Scholar
Broach, James R. Google Scholar
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
platelet-activating factor
neuroinflammation
anti-inflammatory
cytokines
xmlui.dri2xhtml.METS-1.0.item-coverage Lausanne
Language English
Sponsor Brazilian government agencies FAPESP
CNPq
Pennsylvania Department of Health using Tobacco CURE funds
Grant number FAPESP: 2013/07838-0, 2014/25602-6
CNPq: 303905/2013-1
Date 2018
Published in Frontiers In Neurology. Lausanne, v. 9, p. -, 2018.
ISSN 1664-2295 (Sherpa/Romeo, impact factor)
Publisher Frontiers Media Sa
Extent -
Origin http://dx.doi.org/10.3389/fneur.2018.00039
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000424233400002
URI https://repositorio.unifesp.br/handle/11600/54141

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