Protein plays Jekyll and Hyde role in Lou Gehrig's disease

"The protein superoxide dismutase, normally a useful antioxidant, goes from Dr. Jekyll to Mr. Hyde when it clumps up," said Agar. This research indicates that protein aggregation is toxic in ALS, something that has not been proven for other neurodegenerative diseases such as Alzheimer's and Parkinson's, though researchers worldwide are studying the role of protein clumps in these conditions, as well.

Still, scientists disagree on the nature of the toxic gain of function because not all clumps are toxic, nor are they all the same size in patients with neurodegenerative disease, or healthy people, for that matter. But Agar says that large clumps cause cell death, literally exploding the thread-like axons on nerve cells that transmit impulses from the cell.

"Most people are familiar with the process of aggregation, which is what happens when you cook an egg. A fluid (the egg white) is full of proteins that are free to move about. Upon cooking, these proteins unfold and clump together. When this happens inside a cell, especially inside the long, narrow, tubes that connect neurons (axons), the cells essentially choke because they can't move proteins and nutrients to where they are needed. The loss of motor neurons then results in the death of ALS patients."

The next step, said Agar, is to develop drugs that target key proteins and prevent them from clumping together. "Our study used data from innumerous ALS researchers, and the field has been working toward this discovery for some time. My hope is that if our findings are validated by other research groups, molecules that prevent aggregation will be developed and used to treat ALS. We hope to contribute to this process and have initiated the lengthy process of developing such molecules in collaboration with the laboratories of Greg Pestko and Dagmar Ringe here at Brandeis."