(Press-News.org) Two proteins conspire to promote a lethal neurological disease, according to a study published online this week in the Journal of Experimental Medicine (www.jem.org).
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.
Jean-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.
These findings highlight p65 as a potential therapeutic target for this debilitating disorder.
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About The Journal of Experimental Medicine
The Journal of Experimental Medicine (JEM) is published by The Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists in conjunction with our in-house scientific editors. JEM content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works and third parties may reuse the content for non-commercial purposes under a creative commons license. For more information, please visit http://www.jem.org.
Swarup, V., et al. 2011. J. Exp. Med. doi:10.1084/jem.20111313
Potential new drug target in Lou Gehrig's disease
2011-11-15
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