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Lou Gehrig's protein found throughout brain, suggesting effects beyond motor neurons
Date:6/16/2008

PHILADELPHIA - Two years ago researchers at the University of Pennsylvania School of Medicine discovered that misfolded proteins called TDP-43 accumulated in the motor areas of the brains of patients with amyotropic lateral sclerosis (ALS), or Lou Gehrig's disease. Now, the same group has shown that TDP-43 accumulates throughout the brain, suggesting ALS has broader neurological effects than previously appreciated and treatments need to take into account more than motor neuron areas. Their article appeared in last month's issue of the Archives of Neurology.

"The primary implication for ALS patients is that we have identified a molecular target for new therapies," says co-author John Q. Trojanowski, MD, PhD, Director of Penn's Institute on Aging. "The other implication is that new therapies for ALS now need to go beyond treating only motor neurons."

Traditionally, ALS has been diagnosed based on muscle weakness and neurodegeneration of the upper and lower motor neurons that extend from the motor cortex to the spinal cord and brainstem motor neurons, which directly innervate voluntary muscles. For example, if you want to wiggle your big toe, the signal travels from the motor neuron in the cortex at the top of your head to a synapse on the lower spinal cord motor neurons in the lower back, which, in turn transmit the "wiggle" command by sending a signal to the muscles that move your big toe. Patients with ALS cannot wiggle their big toe or complete other voluntary muscle movements, including those carried out by their other extremities and eventually, by the diaphragm that moves air in and of their lungs.

The study was conducted by examining post-mortem brain tissue of 31 ALS patients. The accumulation of TDP-43 was imaged by detecting TDP-43 with an antibody specific for this protein. TDP-43 pathology was observed not only in the areas of the brain and spinal cord that control voluntary movements, as expected, but also in regio
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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