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Removing protein 'garbage' in nerve cells may help control 2 neurodegenerative diseases
Date:12/19/2012

WASHINGTON Neuroscientists at Georgetown University Medical Center say they have new evidence that challenges scientific dogma involving two fatal neurodegenerative diseases amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) and, in the process, have uncovered a possible therapeutic target as a novel strategy to treat both disorders.

The study, posted online today in the Journal of Biological Chemistry, found that the issue in both diseases is the inability of the cell's protein garbage disposal system to "pull out" and destroy TDP-43, a powerful, sometimes mutated gene that produces excess amounts of protein inside the nucleus of a nerve cell, or neuron.

"This finding suggests that if we're able to 'rev up' that clearance machinery and help the cell get rid of the bad actors, it could possibly reduce or slow the development of ALS and FTD," says the study's lead investigator, neuroscientist Charbel E-H Moussa, MB, PhD. "The potential of such an advance is very exciting." He cautions, though, that determining if this strategy is possible in humans could take many years and will involve teams of researchers.

The way to rev up protein disposal is to add parkin the cell's natural disposal units to brain cells. In this study, Moussa and his colleagues demonstrated in two animal experiments that delivering parkin genes to neurons slowed down ALS pathologies linked to TDP-43."

Moussa says that his study further demonstrates that clumps known as "inclusions" of TDP-43 protein found inside neuron bodies in both disorders do not promote these diseases, as some researchers have argued.

What happens in both diseases is that this protein, which is a potent regulator of thousands of genes, leaves the nucleus and collects inside the gel-like cytoplasm of the neuron. In ALS, also known as Lou Gehrig's disease, this occurs in motor neurons, affecting movement; in FTD, it occurs in the frontal lobe of the brain, leadi
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Contact: Karen Mallet
km463@georgetown.edu
Georgetown University Medical Center
Source:Eurekalert

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