SMBA Research: Can This Cell Be Saved?

Nerve-cell defense mechanism may hold key to SBMA treatment

by Quest Staff on January 3, 2009 - 3:13pm

A defense mechanism called “autophagy” that neurons (nerve cells) use to protect themselves from dangerous misfolded proteins may hold the key to developing treatments for spinal-bulbar muscular atrophy (SBMA, or Kennedy disease) and perhaps similar neurodegenerative diseases, new research shows.

Albert La Spada
MDA grantee Albert La Spada and colleagues are studying how cells protect themselves against dangerously misshapen protein molecules.

Autophagy, which means "self-digestion," is used by cells to degrade protein molecules that have folded into dangerous shapes that can cause cell death. (SBMA-affected cells attempt to utilize this mechanism, but it's insufficient in these cells.) Many neurological and neuromuscular diseases involve overproduction of and damage from misfolded protein molecules, because neurons are exquisitely vulnerable to misfolded protein stress.

Until now, studying autophagy with the aim of exploiting its possible therapeutic effects has been technically difficult, and attempts to induce it in the laboratory have destroyed cells.

But 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 autophagy. They published their findings online Nov. 18 in the Journal of Biological Chemistry.

La Spada and colleagues found that 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.

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