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

Detalhes bibliográficos
Autor(a) principal: Briones, Marcelo R. S. [UNIFESP]
Data de Publicação: 2018
Outros Autores: Snyder, Amanda M., Ferreira, Renata C. [UNIFESP], Neely, Elizabeth B., Connor, James R., Broach, James R.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: http://dx.doi.org/10.3389/fneur.2018.00039
https://repositorio.unifesp.br/handle/11600/54141
Resumo: 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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spelling A Possible role for Platelet-Activating Factor receptor in Amyotrophic Lateral sclerosis treatmentamyotrophic lateral sclerosisplatelet-activating factorneuroinflammationanti-inflammatorycytokinesAmyotrophic 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.Univ Fed Sao Paulo, Dept Hlth Informat, Escola Paulista Med, Sao Paulo, SP, BrazilPenn State Coll Med, Inst Personalized Med, Dept Biochem, Hershey, PA 17033 USAPenn State Coll Med, Dept Neurosurg, Hershey, PA USAUniv Fed Sao Paulo, Escola Paulista Med, Dept Neurol & Neurosurg, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Hlth Informat, Escola Paulista Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Neurol & Neurosurg, Sao Paulo, SP, BrazilWeb of ScienceBrazilian government agencies FAPESPCNPqPennsylvania Department of Health using Tobacco CURE fundsFAPESP: 2013/07838-0, 2014/25602-6CNPq: 303905/2013-1Frontiers Media Sa2020-07-08T13:09:41Z2020-07-08T13:09:41Z2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion-application/pdfhttp://dx.doi.org/10.3389/fneur.2018.00039Frontiers In Neurology. Lausanne, v. 9, p. -, 2018.10.3389/fneur.2018.00039WOS000424233400002.pdf1664-2295https://repositorio.unifesp.br/handle/11600/54141WOS:000424233400002engFrontiers In NeurologyLausanneinfo:eu-repo/semantics/openAccessBriones, Marcelo R. S. [UNIFESP]Snyder, Amanda M.Ferreira, Renata C. [UNIFESP]Neely, Elizabeth B.Connor, James R.Broach, James R.reponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-11T05:40:42Zoai:repositorio.unifesp.br/:11600/54141Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-11T05:40:42Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv A Possible role for Platelet-Activating Factor receptor in Amyotrophic Lateral sclerosis treatment
title A Possible role for Platelet-Activating Factor receptor in Amyotrophic Lateral sclerosis treatment
spellingShingle A Possible role for Platelet-Activating Factor receptor in Amyotrophic Lateral sclerosis treatment
Briones, Marcelo R. S. [UNIFESP]
amyotrophic lateral sclerosis
platelet-activating factor
neuroinflammation
anti-inflammatory
cytokines
title_short A Possible role for Platelet-Activating Factor receptor in Amyotrophic Lateral sclerosis treatment
title_full A Possible role for Platelet-Activating Factor receptor in Amyotrophic Lateral sclerosis treatment
title_fullStr A Possible role for Platelet-Activating Factor receptor in Amyotrophic Lateral sclerosis treatment
title_full_unstemmed A Possible role for Platelet-Activating Factor receptor in Amyotrophic Lateral sclerosis treatment
title_sort A Possible role for Platelet-Activating Factor receptor in Amyotrophic Lateral sclerosis treatment
author Briones, Marcelo R. S. [UNIFESP]
author_facet Briones, Marcelo R. S. [UNIFESP]
Snyder, Amanda M.
Ferreira, Renata C. [UNIFESP]
Neely, Elizabeth B.
Connor, James R.
Broach, James R.
author_role author
author2 Snyder, Amanda M.
Ferreira, Renata C. [UNIFESP]
Neely, Elizabeth B.
Connor, James R.
Broach, James R.
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Briones, Marcelo R. S. [UNIFESP]
Snyder, Amanda M.
Ferreira, Renata C. [UNIFESP]
Neely, Elizabeth B.
Connor, James R.
Broach, James R.
dc.subject.por.fl_str_mv amyotrophic lateral sclerosis
platelet-activating factor
neuroinflammation
anti-inflammatory
cytokines
topic amyotrophic lateral sclerosis
platelet-activating factor
neuroinflammation
anti-inflammatory
cytokines
description 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.
publishDate 2018
dc.date.none.fl_str_mv 2018
2020-07-08T13:09:41Z
2020-07-08T13:09:41Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.3389/fneur.2018.00039
Frontiers In Neurology. Lausanne, v. 9, p. -, 2018.
10.3389/fneur.2018.00039
WOS000424233400002.pdf
1664-2295
https://repositorio.unifesp.br/handle/11600/54141
WOS:000424233400002
url http://dx.doi.org/10.3389/fneur.2018.00039
https://repositorio.unifesp.br/handle/11600/54141
identifier_str_mv Frontiers In Neurology. Lausanne, v. 9, p. -, 2018.
10.3389/fneur.2018.00039
WOS000424233400002.pdf
1664-2295
WOS:000424233400002
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Frontiers In Neurology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv -
application/pdf
dc.coverage.none.fl_str_mv Lausanne
dc.publisher.none.fl_str_mv Frontiers Media Sa
publisher.none.fl_str_mv Frontiers Media Sa
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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