New drug target for Alzheimer's identified

Scientists have identified a potential new drug target in the shape of a protein for the neurodegenerative disease Alzheimer's.

PTI| Last Updated: Aug 19, 2015, 13:25 PM IST

Washington: Scientists have identified a potential new drug target in the shape of a protein for the neurodegenerative disease Alzheimer's.

Toxic protein fragments known as amyloid-beta clumped together between neurons in a person's brain are a hallmark of Alzheimer's.

Neurons themselves make amyloid-beta, and for reasons that aren't fully understood, its accumulation ultimately contributes to the memory loss, personality changes, and other symptoms that patients with this degenerative disease often suffer from.

New research by Rockefeller University scientists and their colleagues have identified a series of naturally occurring molecular steps - known as a pathway - that can dampen the production of amyloid-beta.

These results suggest a new route in the search for Alzheimer's therapies.

"Our discovery centres on a protein called WAVE1, which we found to be important in the production of amyloid-beta. The reduction of WAVE1 appears to have a protective effect against the disease," said study author Paul Greengard, Vincent Astor Professor and head of the Laboratory of Molecular and Cellular Neuroscience.

"When levels of amyloid-beta rise, there is an accompanying increase in another molecule, AICD, which reduces the expression of WAVE1. This has the effect of reducing the production of amyloid-beta," said Greengard.

"By targeting steps within this newly discovered pathway," he added, "it may be possible to develop drugs to reduce amyloid-beta that potentially could be used to either treat or prevent Alzheimer's disease."

WAVE1 is known to help to build filaments of a protein called actin that serve as basic components of cellular structures.

In the current study, the team, including first author Ilaria Ceglia, who conducted this work while a research associate in the lab, examined the levels of WAVE1 in mouse and cellular models of Alzheimer's disease and found that they were unusually low.

Research done by a collaborator at Columbia University found this was also true for the brains of human patients with the disease.

To take a closer look at the relationship between amyloid-beta and WAVE1, the researchers tested the brains and memories of mice genetically altered to produce high levels of amyloid-beta and varying levels of WAVE1.

They found a dose-dependent response: Mice brains with low WAVE1 levels produced less amyloid-beta, and these animals performed better on memory tests.

The study was published in the journal Nature Medicine.