Columbia U. scientists spotlight a promising proteasome approach in preventing Alzheimer's

Proteasomes play a big role in promoting a healthy brain. The hollow structures work as a janitor, chewing up defective proteins and then recycling them into new proteins needed by cells.

Working with funding from the NIH, a group of scientists at Columbia University showed that the buildup of a toxic protein in the brain linked to Alzheimer's is associated with reduced proteasome activity. And working with mouse models, they go on to say that a new drug that amps up proteasome activity has real potential for slowing down or stopping disease progression, provided you start at a very early stage.

To do this in mice, the investigators used an antidepressant called rolipram. Rolipram has side effects that prevent its use in humans and won't work as a prospective drug for Alzheimer's. But in mice the drug blocked an enzyme that reduces cyclic AMP, which they believe is critical for regulating proteasome activity.

Tested on brain slices from the mice, the drug worked in triggering new proteasome activity, cleaning up the toxic protein tau, which is considered a likely suspect--along with amyloid beta--in triggering the disease. The results were published this week in Nature Medicine.

Now the team wants to study libraries of drug compounds to see if they can find a safe one that accomplishes the required task. And they say that the same approach may prove promising in other neurodegenerative diseases as well.

"The proteasome system we are studying also degrades proteins associated with a number of other neurodegenerative diseases such as Parkinson's, Huntington's, frontotemporal degeneration and amyotrophic lateral sclerosis," said Karen Duff, a professor of pathology and cell biology at Columbia University, in a statement. "We may be able to apply these findings to other disorders that accumulate proteins."

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