May 10, 2007

Protein’s Role Emerging in ALS and Cognitive Change

[Quick Summary: The protein discovered to be a potential common link in ALS and frontotemporal dementia is thought to interact with the genetic message instructing how to assemble components within motor neurons, an aspect of the disease process that could provide therapeutic targets.]

Researchers led by Canadian investigator Michael Strong, M.D., published in Molecular and Cellular Neurosciences that a protein newly implicated in amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease) alters the message that directs construction of the scaffold inside motor neurons. This gives a new focus to the effort to find effective treatment for the disease.

ALS and a kind of cognitive change called frontotemporal dementia can occur in the same patients. Research that is revealing common aspects of these disorders has accelerated, and the progress reported here ties together several threads.

The scientists at Robarts Research Institute and The University of Western Ontario, funded in part by The ALS Association, found that the protein, called TDP-43, interacts directly with the messenger that carries genetic instructions that allow the motor neuron to carry out internal tasks.

The investigators propose that TDP-43 preserves the messenger (mRNA) directing construction of the neurofilaments. These scaffolded proteins in turn allow transport of key cell materials from the nerve cell body in the spinal cord to its distant endings on muscle.

"It certainly opens the door for consideration that changes in RNA messages are involved in ALS and links in prior findings by ourselves and others that neurofilaments are important to the disease process,” said Strong.

The results also suggest how mutant copper-zinc superoxide dismutase (SOD1), a protein change responsible for some inherited forms of ALS, might act similarly to TDP-43.

Strong and colleagues suggest both TDP-43 and mutant SOD1 may affect the proper ratio of neurofilaments by changing the messages guiding their manufacture and thereby disrupt the transport of materials that are the key to maintaining motor neuron health. Importantly, this might provide a common mechanism for both inherited and spontaneously arising cases of ALS. This emerging area in the search for ALS therapeutics will require further validation to see in what precise way the findings relate to the disease process.

The project is jointly funded by The ALS Association and the ALS Society of Canada.

Learn more about cognitive change in ALS.

Click here for the PubMed article.