A Possible role for Platelet-Activating Factor receptor in Amyotrophic Lateral sclerosis treatment
Autor(a) principal: | |
---|---|
Data de Publicação: | 2018 |
Outros Autores: | , , , , |
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. |
id |
UFSP_f45349c1dea4c155e574fc13a164d780 |
---|---|
oai_identifier_str |
oai:repositorio.unifesp.br/:11600/54141 |
network_acronym_str |
UFSP |
network_name_str |
Repositório Institucional da UNIFESP |
repository_id_str |
3465 |
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 |
_version_ |
1814268413616324608 |