November 14, 2011. – A research team from Université Laval, led by Jean-Pierre Julien, has taken a new step in understanding the cellular mechanisms involved in Lou Gehrig’s disease, also known as amyotrophic lateral sclerosis (ALS). This disease is characterized by degeneration of neurons that control muscle activity.
By studying the spinal cord of people who died from ALS, the research team has discovered that there was overproduction of a protein called TDP-43 in their nervous tissue. The researchers have also shown that TDP-43 interacts with a key protein of the immune system, NF-kB. “Overexpression of TDP-43 leads to an exaggerated inflammatory response that increases the vulnerability of neurons to neurotoxic molecules that circulate in the body,” says Jean-Pierre Julien, professor at the Faculty of Medicine of Université Laval and a researcher at CRCHUQ . The protein NF-kB plays a central role in the regulation of many genes involved in immune response and inflammation. There are many inhibitors of this protein. The team tested an inhibitor of the NF-kB signaling pathway, withaferin A, in transgenic mice that express the main symptoms of ALS. “This drug has proved effective to reduce inflammation, improve motor control and partially restore the neuromuscular junction,” said Professor Julien.
Dr. Julien will continue searching for an inhibitor that would prevent TDP-43 from acting on NF- κB, without compromising the role NF-κB plays in defending the body. The work summarized here, was published in the Nov. 14 online edition of the Journal of Experimental Medicine.
About Lou Gehrig’s disease: Lou Gehrig’s disease, also known as amyotrophic lateral sclerosis (ALS), is characterized by degeneration of neurons that control muscle activity. The damage to motor neurons, whose first manifestations occur in adulthood, causes a progressive weakening of the arms and legs, followed by muscle paralysis and a few years later by severe breathing problems that lead to death . There is still no treatment to stop this disease that strikes 5 to 7 people per 100 000 population.
Source of text and image: Jean Hamann and Hélène Mélançon, Université Laval Translation: Canadian Association for Neuroscience (J. Poupart)
