Scientists at Northwestern University report a surprising discovery that offers a possible new route for the treatment of neurodegenerative diseases. In a study of the transparent roundworm C. elegans, they found that a genetic switch in master neurons inhibits the proper functioning of protective cell stress responses, leading to the accumulation of misfolded and damaged proteins.
Neurodegenerative diseases, ranging from Huntington's and Parkinson's to amyotrophic lateral sclerosis and Alzheimer's, are believed to stem from early events that lead to an accumulation of damaged proteins in cells. Yet all animals, including humans, have an ancient and very powerful mechanism for detecting and responding to such damage, known as the heat shock response.
"Why are these diseases so widespread if our cells have ways to detect and prevent damaged proteins from accumulating?" said Richard I. Morimoto, who led the research together with postdoctoral colleague Veena Prahlad. "Can our body fix the problem? That is the conundrum."
"In our study, much to our surprise, we discovered that the nervous system sends negative signals to other tissues in the animal that inhibit the ability of cells to activate a protective heat shock response," Morimoto said. "The machinery to repair the damaged proteins is intact, but the nervous system is sending a signal that prevents it from doing its job."
When the signal from the nervous system was reduced, the cells' heat shock response returned, leading to elevated levels of special protective proteins, called molecular chaperones, that kept the damaged proteins in check.
Morimoto is the Bill and Gayle Cook Professor of Biology in the department of molecular biosciences and the Rice Institute for Biomedical Research in Northwestern's Weinberg College of Arts and Sciences.
The findings are published by the Proceedings of the National Academy of Sciences (PNAS).
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