Jan. 5, 2009

Researchers Explore Self-Defense in Nerve Cells

Revving up a natural cellular defense mechanism that neurons (nerve cells) use to protect themselves looks like a good lead in developing treatments for spinal-bulbar muscular atrophy (SBMA, or Kennedy disease) and perhaps similar neurodegenerative diseases, new research shows.

MDA grantee Albert La Spada and co-workers at the University of Washington Medical Center in Seattle recently found a new and convenient way to study the defense mechanism known as "autophagy." They published their findings online Nov. 18 in the Journal of Biological Chemistry.

Autophagy, which means "self-digestion," is used by cells to degrade protein molecules that have folded into a dangerous shape and can cause cell death. (SBMA-affected cells attempt to utilize this mechanism, but insufficiently.) Many neurological and neuromuscular diseases involve the production of misfolded protein molecules because neurons are highly vulnerable to misfolded protein stress.

Until now, studying autophagy, with the aim of exploiting it for its possible therapeutic effects, has been technically difficult, and attempts to induce it in the laboratory have destroyed cells. But La Spada and colleagues have found depriving neurons of certain nutrients while they're being maintained in the lab can induce autophagy without killing the cells, giving the researchers a valuable window on the process.

They found that, in the laboratory, neurons producing misfolded androgen receptor protein molecules, which cause cell death in SBMA, were protected by enhanced autophagy after they were deprived of selected nutrients.

Knowing more about this neuroprotective pathway and how it might be enhanced in disease-affected neurons "will better guide strategies for therapy development," the researchers say.