| First Author | Frakes AE | Year | 2014 |
| Journal | Neuron | Volume | 81 |
| Issue | 5 | Pages | 1009-1023 |
| PubMed ID | 24607225 | Mgi Jnum | J:213059 |
| Mgi Id | MGI:5582838 | Doi | 10.1016/j.neuron.2014.01.013 |
| Citation | Frakes AE, et al. (2014) Microglia induce motor neuron death via the classical NF-kappaB pathway in amyotrophic lateral sclerosis. Neuron 81(5):1009-23 |
| abstractText | Neuroinflammation is one of the most striking hallmarks of amyotrophic lateral sclerosis (ALS). Nuclear factor-kappa B (NF-kappaB), 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-kappaB inhibition in ALS astrocytes is not sufficient to rescue motor neuron (MN) death. However, the localization of NF-kappaB activity and subsequent deletion of NF-kappaB 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-kappaB 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. |
