Suchergebnisse

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. ; Brazilian government agencies FAPESP ; CNPq ; Pennsylvania Department of Health using Tobacco CURE funds ; Univ Fed Sao Paulo, Dept Hlth Informat, Escola Paulista Med, Sao Paulo, SP, Brazil ; Penn State Coll Med, Inst Personalized Med, Dept Biochem, Hershey, PA 17033 USA ; Penn State Coll Med, Dept Neurosurg, Hershey, PA USA ; Univ Fed Sao Paulo, Escola Paulista Med, Dept Neurol & Neurosurg, Sao Paulo, SP, Brazil ; Univ Fed Sao Paulo, Dept Hlth Informat, Escola Paulista Med, Sao Paulo, SP, Brazil ; Univ Fed Sao Paulo, Escola Paulista Med, Dept Neurol & Neurosurg, Sao Paulo, SP, Brazil ; FAPESP: 2013/07838-0, 2014/25602-6 ; CNPq: 303905/2013-1 ; Web of Science