Researchers have identified p65 protein as a potential therapeutic target for amyotrophic lateral sclerosis. The findings published this week in the Journal of Experimental Medicine .
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a devastating neurodegenerative disorder that results in progressive loss of motor function and ultimately death. More than 90% of ALS cases have no known genetic cause or family history. However, in some patients, spinal cord cells contain unusual accumulations of a protein called TDP-43.
AdvertisementJean-Pierre Julien and colleagues at Laval University in Quebec now find that TDP-43 binds to an inflammatory protein called NF-kB p65 in the spinal cords of ALS patients but not of healthy individuals. TDP-43 and p65 were also more abundant in ALS than healthy spinal cords. In spinal cord cells called microglia, TDP-43 and p65 cooperated to ramp up production of factors capable of promoting inflammation and killing nearby neurons. In a mouse model of ALS, treatment with an agent capable of blocking p65 activity minimized neuron loss and eased disease symptoms.
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