New research conducted by scientists at the Columbia University Medical Center revealed that the drug rolipram can effectively boost the brain's "garbage disposal" system and help it decrease levels of toxic proteins that are associated with Alzheimer's disease, as well as improve cognition, in mice. Although rolipram causes nausea and is not a good candidate for the treatment of neurodegenerative disorders in humans, similar drugs have the potential to go to clinical trials in the near future.
"We have shown for the first time that it's possible to use a drug to activate this disposal system in neurons and effectively slow down disease," said Karen Duff, who headed the research, in a press release. "This has the potential to open up new avenues of treatment for Alzheimer's and many other neurodegenerative diseases."
The researchers used a mouse model of neurodegeneration and discovered that tau, the toxic protein linked to Alzheimer's and various other neurodegenerative diseases, is at the root of the decreased protein disposal process that underlies these diseases. Typically, proteasomes are responsible for the disposal of cell waste, but tau inhibits this process by sticking to them.
The scientists found that administering rolipram activated the proteasomes in mice and brought disposal levels back to normal, as well as increased the memory of diseased mice to normal levels.
The findings point to the importance of finding drugs that target proteasomes and increase their effectiveness in others to prevent and improve the detrimental effects suffered by those with neurodegenerative diseases.
"This exciting research from Dr. Duff's team advances our basic understanding of the proteasome system, provides a way to repair the system when it breaks, and alleviates symptoms of neurodegenerative disorders," said Rod Corriveau of the National Institute of Health's National Institute of Neurological Disorders and Stroke, which provided funding for the study.
The findings were published in the Dec. 21 issue of Nature Medicine.
