Enzyme family plays role in Alzheimer's

The route to a treatment for Alzheimer's disease may have become more straightforward with the discovery that a key enzyme known to have a major role in this disease is in fact part of a family of enzymes. Only some family members play a role in the progression of this brain-wasting illness, new research at the University of Toronto has found.

"It was previously thought that an enzyme called gamma-secretase contributed to the development of protein deposits in the Alzheimer's brain. This study shows that this enzyme is more accurately described as a family of enzymes, each with its own specialization," explains Professor David Westaway of U of T's Centre for Research in Neurodegenerative Diseases and senior author of a paper in the June 21 issue of the Proceedings of the National Academy of Sciences.

Gamma-secretase enzymes generate toxic molecules called amyloid-beta peptides. These peptides produce deposits called amyloid plaques, the brain lesions that are a defining feature of Alzheimer's disease. If scientists can stop these enzymes from working, they will be able to stop their resulting toxic molecules from forming in the brain. Complicating the situation is the fact that the gamma-secretase enzyme was also thought to be involved in healthy functioning of other tissues; therefore, therapies would have to inhibit the negative effects while maintaining the normal functioning of other cells.

Westaway and his research colleagues used genetically-engineered mice to show that toxic activity of gamma-secretase could be separated from its other benign activities.

"This finding provides hope that Alzheimer's treatments can be developed that reduces toxic activity of certain gamma-secretases while still maintaining the beneficial activities of other family members," says Peter Mastrangelo, a research associate in Westaway's lab and first author of the paper.

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