Microglia, macrophages of the brain and spinal cord, are critical for protecting the central nervous system against invading pathogens. However, they are also central contributors to neuroinflammation and motor neuron death in ALS. A new study, published in Neuron on March 5 online from Brian Kaspar’s laboratory at the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, describes a novel mechanism for microglia-induced inflammation via NF-κB. This proinflammatory transcription factor is upregulated in the spinal cord of ALS patients and of SOD1-G93A mice. The researchers demonstrate that selective inhibition of NF-κB in microglia slows disease progression in the ALS mouse model by 47%, while inhibition in astrocytes alone has little effect. Interestingly, NF-kB has already been implicated in ALS through interactions with the ALS-associated protein, TDP-43 (see December 2011 story). Together, these finding suggest that NF-kB may be a promising therapeutic target for inhibiting microglia-induced inflammation in ALS. Click here to read more.
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