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Alzheimer's disease as a case of brake failure?
Date:6/24/2008

NEW BRUNSWICK, N.J. Rutgers researcher Karl Herrup and colleagues at Case Western Reserve University have discovered that a protein that suppresses cell division in brain cells effectively "puts the brakes" on the dementia that comes with Alzheimer's disease (AD). When the brakes fail, dementia results.

This discovery could open the door to new ways of treating Alzheimer's disease, which affects up to half the population over the age of 85.

Determining the protein's previously unsuspected role in AD is an important piece of the puzzle and it brings a new perspective to the basis of AD. "It changes the logic from a search for a trigger that kicks off the dementia to the failure of a safety that has suppressed it," Herrup said.

The researchers reported their findings in the in the June 24 Proceedings of the National Academy of Sciences (PNAS). The paper was previously available online in the PNAS Early Edition.

Herrup has spent a good part of his career seeking to unravel the mystery behind unrestrained cell cycling. Looking at AD through the lens of cancer, Herrup sees the rampant cell division associated with cancer mirrored in AD-related dementia.

In cancer, the seemingly uncontrollable cell division enables the disease to overwhelm normal body cells. Adult neurons, or nerve cells, don't normally divide. (Cancerous brain tumors do not grow from neurons but from glial cells.) Instead of producing new neurons in the brain, the cycling leads to cell death, which causes progressive dementia.

"Every cell wants to divide, and that basic urge never leaves the cell," Herrup said.

"Homeostasis in the brain has worked out a way to successfully suppress cell cycling, but with age even that highly successful program sometimes fails, resulting in a catastrophic loss of neurons."

Herrup's team experimented with a protein family known as cyclin-dependent kinases (Cdk). These enzymes power the cel
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Contact: Joseph Blumberg
blumberg@ur.rutgers.edu
732-932-7084 x652
Rutgers University
Source:Eurekalert

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