Rock Creek Pharmaceuticals Inc. (fka RCPIQ)

[Buddhahead]

Microglia induce motor neuron death via the classical NF-?B pathway in amyotrophic lateral sclerosis at Pub Med, Frakes AE1, Ferraiuolo L2, Haidet-Phillips AM2, Schmelzer L2, Braun L2, Miranda CJ2, Ladner KJ3, Bevan AK1, Foust KD4, Godbout JP4, Popovich PG4, Guttridge DC3, Kaspar BK5.
Author information
1Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA; Biomedical Sciences Graduate Program, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
2Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
3Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA.
4Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA.
5Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA; Biomedical Sciences Graduate Program, College of Medicine, The Ohio State University, Columbus, OH 43210, USA; Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA. Electronic address: [e-mail]., March 2014

Abstract:
"Neuroinflammation is one of the most striking hallmarks of amyotrophic lateral sclerosis (ALS). Nuclear factor-kappa B (NF-?B), a master regulator of inflammation, is upregulated in spinal cords of ALS patients and SOD1-G93A mice. In this study, we show that selective NF-?B inhibition in ALS astrocytes is not sufficient to rescue motor neuron (MN) death. However, the localization of NF-?B activity and subsequent deletion of NF-?B signaling in microglia rescued MNs from microglial-mediated death in vitro and extended survival in ALS mice by impairing proinflammatory microglial activation. Conversely, constitutive activation of NF-?B selectively in wild-type microglia induced gliosis and MN death in vitro and in vivo. Taken together, these data provide a mechanism by which microglia induce MN death in ALS and suggest a novel therapeutic target that can be modulated to slow the progression of ALS and possibly other neurodegenerative diseases by which microglial activation plays a role.
Copyright © 2014 Elsevier Inc. All rights reserved."

Article at:
http://www.ncbi.nlm.nih.gov/pubmed/24607225