BOSTON--Scientists at Dana-Farber Cancer Institute and Harvard Medical School have found that a common cancer protein leads a second, totally different life in normal adult brain cells: It helps regulates memory formation and may be implicated in Alzheimer's disease.
Cyclin E is a well-known culprit that drives many types of solid tumors and blood cancers. The report, published online in Developmental Cell, is the first revelation that cyclin E has a crucial role in the formation of nerve connections, or synapses, in the brain. Synapses are tiny connections between brain cells where memories are stored.
"This protein has a double life," said Peter Sicinski, PhD, a cancer biologist at Dana-Farber and senior author of the publication. "It is overexpressed in many different cancers, but it also is expressed in high levels in the human brain. We have found that cyclin E is needed for memory formation and is a very important player."
The researchers found potential evidence linking cyclin E to Alzheimer's disease, because it binds to an enzyme called Cdk5 that is involved in memory.
"There is good evidence that hyperactivity of Cdk5 contributes to Alzheimer's disease and inhibiting this enzyme can ameliorate symptoms in animals," said Sicinski, who is also a professor of Genetics at Harvard Medical School. "Manipulating cyclin E levels might be another way to accomplish this."
The scientists didn't test cyclin E in Alzheimer's mice, but they did show that when cyclin E binds to Cdk5 molecules, it locks them away in an unusable form. Moreover, when the researchers reduced cyclin E levels in mouse brain cells, fewer nerve connections formed and the animals' memories suffered.
Cyclins are a family of related proteins found in dividing cells. They serve as biological switches, controlling a cell's progression from one phase of its life cycle to the next. The actual signals to exit one phase and enter the nex
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Dana-Farber Cancer Institute