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Could boosting brain cells' appetites fight disease? New research shows promise

ANN ARBOR, Mich. Deep inside the brains of people with dementia and Lou Gehrig's disease, globs of abnormal protein gum up the inner workings of brain cells dooming them to an early death.

But boosting those cells' natural ability to clean up those clogs might hold the key to better treatment for such conditions.

That's the key finding of new research from a University of Michigan Medical School physician scientist and his colleagues in California and the United Kingdom. They reported their latest findings this week in the journal Nature Chemical Biology.

Though the team showed the effect worked in animals and human neurons from stem cells, not patients, their discoveries point the way to find new medicines that boost the protein-clearing cleanup process.

The work also shows how an innovative microscope technique can help researchers see what's going on inside brain cells, as they labor to clear out the protein buildup.

The researchers focused on a crucial cell-cleaning process called autophagy a hot topic in basic medical research these days, as scientists discover its important role in many conditions. In autophagy, cells bundle unwanted materials up, break them down and push the waste products out.

In the newly published research, the team showed how the self-cleaning capacity of some brain cells gets overwhelmed if the cells make too much of an abnormal protein called TDP43. The found that cells vary greatly in how quickly their autophagy capacity gets swamped.

But they also showed how three drugs that boost autophagy speeding up the clean-out process could keep the brain cells alive longer.

Longer-living, TDP43-clearing brain cells are theoretically what people with Lou Gehrig's disease (amyotrophic lateral sclerosis or ALS) and certain forms of dementia (called frontotemporal) need. But only further research will show for sure.

Sami Barmada, M.D.,

Contact: Kara Gavin
University of Michigan Health System

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