Protein that puts the brakes on Alzheimer’s-related dementia identified

June 25th, 2008 - 12:54 pm ICT by ANI  

Washington, June 25 (ANI): In a breakthrough study, researchers at Case Western Reserve University have discovered that a protein called cyclin-dependent kinase5 (Cdk5), which curbs cell division in brain cells, is responsible for putting brakes on the dementia characterised by Alzheimer’s disease (AD).

The researchers also found that when the brakes fail, dementia results.

The discovery by Rutgers researcher Karl Herrup and colleagues may pave the way for new ways of treating Alzheimer’s disease, which affects up to half the population over the age of 85. Finding out Cdks previously unexplained role in AD may offer new insights in 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, said Herrup, chair of the Department of Cell Biology and Neuroscience at Rutgers , The State University of New Jersey.

Herrup, who has long been seeking to unravel the mystery behind unrestrained cell cycling, is now looking at AD through the lens of cancer, and said that rampant cell division is linked with cancer mirrored in AD-related dementia.

In cancer, the seemingly uncontrollable cell division enables the disease to engulf 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. 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, said Herrup.

Herrup’s team experimented the protein family cyclin-dependent kinases (Cdk). These enzymes power the cell cycle, driving it forward through its various phases.

The scientists focused on one particular kinase Cdk5 termed “an atypical kinase” because they could find no involvement in propelling the cell cycle. They found that while it appears to be inert as a cell cycle promoter, Cdk5 in the nervous system actually functions to hold the cell cycle in check.

“Its mere presence helps protect the brain,” Herrup said. “What we discovered is that Cdk5 acts as a brake, not a driver.”

In their laboratory research, they examined the workings of Cdk5 in human AD tissues and in a mouse model. Normally, the protein resides in the nerve cell nucleus, but in the presence of AD both in the mouse model and in the human tissue the disease process drives the protein out into the cell’s cytoplasm. This disrupts the status quo, overrides the brake and unleashes a chain of events that ultimately leads to the death of the cells and the resulting dementia.

“The ejection of Cdk5 out of the nucleus is probably related to the changed chemistry of the Alzheimer’s brain and chronic inflammation that accompanies AD,” said Herrup.

The researchers reported their findings in the in the latest issue of Proceedings of the National Academy of Sciences (PNAS). (ANI)

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