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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Briones, Marcelo R. S. [1, 2] ; Snyder, Amanda M. [3] ; Ferreira, Renata C. [4] ; Neely, Elizabeth B. [3] ; Connor, James R. [3] ; Broach, James R. [1]
Total Authors: 6
Affiliation:
[1] Penn State Coll Med, Inst Personalized Med, Dept Biochem, Hershey, PA 17033 - USA
[2] Univ Fed Sao Paulo, Dept Hlth Informat, Escola Paulista Med, Sao Paulo, SP - Brazil
[3] Penn State Coll Med, Dept Neurosurg, Hershey, PA - USA
[4] Univ Fed Sao Paulo, Escola Paulista Med, Dept Neurol & Neurosurg, Sao Paulo, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: FRONTIERS IN NEUROLOGY; v. 9, FEB 6 2018.
Web of Science Citations: 1
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. (AU)

FAPESP's process: 13/07838-0 - Mitochondrial microdiversity of Candida albicans and its implications in hospital-acquired infections and patterns of mitochondrial genome macroevolution
Grantee:Marcelo Ribeiro da Silva Briones
Support type: Regular Research Grants
FAPESP's process: 14/25602-6 - Mitochondrial genomics of amyotrophic lateral sclerosis
Grantee:Marcelo Ribeiro da Silva Briones
Support type: Scholarships abroad - Research