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

ns of the brain that involve cognition, executive functioning, memory, and involuntary muscle control. TDP-43 pathology was not observed in any of the controls that did not have ALS.

The pathological TDP-43 observed in ALS brains is different in two ways from normal TDP-43 that is found in most cells. The ALS-associated TDP-43 includes fragments of normal TDP-43 as well as other abnormally modified forms of TDP-43, and it is located in the cytoplasm of neurons; whereas, normal TDP-43 is found almost exclusively in the cell nucleus. In ALS, the pathological TDP-43 accumulates in large "globs," mainly in cell bodies.

"Our observation of TDP-43 in the brains of ALS patients suggests that ALS and two other neurodegenerative diseases called ALS- PLUS [ALS with cognitive impairments] and FTLD [frontotemporal lobar disease] may all have the same underlying molecular pathology involving abnormal TDP-43," says Trojanowski. "This constitutes a paradigm shift in the way we think about these diseases."

Current research is focused on understanding the basic biology of TDP-43 in cell culture systems. The research team is now trying to find out whether pathological TDP-43 causes nerve cells to lose their normal function or if they take on a toxic function. "The over-riding goal that drives our work is helping ALS patients," says Trojanowski.


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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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