In a first, researchers have shown that a drug that boosts activity in the brain’s “garbage disposal” system can decrease levels of toxic proteins associated with Alzheimer’s disease and other neurodegenerative disorders.
“We have shown for the first time that it is possible to use a drug to activate this disposal system in neurons and effectively slow down disease,” said study leader Karen Duff, professor at Columbia University Medical Centre in the US.
“This has the potential to open up new avenues of treatment for Alzheimer’s and many other neurodegenerative diseases,” Duff noted.
The drug used was rolipram, which causes nausea and thus is not a good drug for use in humans, but similar drugs do not incur nausea as a side effect and could go into clinical trials very quickly.
To remain healthy, brain cells must continually clear out old, worn, or damaged proteins, a task performed by a small molecular cylinder called the proteasome.
The proteasome acts as a kind of garbage disposal, grinding up the old proteins so they can be recycled into new ones.
In neurodegenerative diseases, proteins tagged for destruction accumulate in the brain’s neurons, suggesting that the cell’s proteasomes are impaired.
Using a mouse model of neurodegeneration, the researchers first discovered that tau – a toxic protein that accumulates in Alzheimer’s and other brain degenerative diseases – sticks to the proteasome and slows down the protein disposal process.
Administering rolipram activated the proteasome and restored protein disposal to normal levels. The drug also improved the memory of diseased mice to levels seen in healthy mice.
The study was published in the online edition of the journal Nature Medicine.