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Fly mutation suggests link to human brain disease

21.02.2003


Greater insight into human brain disease may emerge from studies of a new genetic mutation that causes adult fruit flies to develop symptoms akin to Alzheimer’s disease.

“This is the first fruit fly mutant to show some of the outward, physical manifestations common to certain major human neurodegenerative diseases,” said principal investigator Michael McKeown, a biology professor at Brown University.

A research team found the mutation in a gene they named “blue cheese.” Reporting in the Feb. 15 issue of the Journal of Neuroscience, the researchers describe blue cheese mutations that lead normal-appearing adult flies (genus Drosophila) to die early from extensive cell death in the brain, neural degeneration, and build-up of protein aggregates.



“These aggregates contain the Drosophila version of proteins that are the major components of plaques that form in the brains of human Alzheimer’s patients,” said the study’s lead author, biologist Kim D. Finley, of the Salk Institute for Biological Studies. “The presence of these proteins in human plaques is at times used as a diagnostic tool for Alzheimer’s disease.”

Genes first identified in Drosophila are often named for a mutant characteristic, said Finley. “The first obvious feature that we noted in older mutant flies was the slow accumulation of dark protein aggregates throughout the brain,” she said. “This reminded us of moldy versions of marbled and veined cheeses, thus the name blue cheese.”

The protein encoded by blue cheese also identifies a new family of proteins present in humans and other vertebrates, as well as in flies, said McKeown. “Our work on blue cheese not only identifies a gene needed for adult neural survival, it also allows identification of the members of this new family,” he said.

Similar blue cheese genes are found in species ranging from worms to humans. The protein encoded by blue cheese – the “blue cheese protein” – may be involved in transport or degradation of proteins and in other brain functions, said the researchers. Fruit flies have similar, yet fewer genes, compared to humans. One of the quickest ways to learn about potential effects of genetic mutations in humans is to screen and sample mutant fly genes.

“Drosophila models have been developed that mimic many aspects of human neural degeneration, primarily by expression of mutant proteins known to cause disease in humans,” said Finley. “In turn these models have been used to identify additional genes involved with the degenerative process, allowing new insights that may result in potential treatments of these disorders.”

In many aspects of gene regulation, growth, differentiation and cell function, Drosophila and human proteins appear very similar and have highly similar actions, said McKeown.

“These observations alone suggest a high likelihood that alterations in human blue cheese will contribute to some degenerative disorders in humans,” he said. In fact, “analysis of the human genetic map shows that blue cheese gene is in a region associated with several familial neurodegenerative diseases,” said McKeown.

For information from the Salk Institute for Biological Studies, contact Robert Bradford, senior director for communications, at (858) 453-4100, ext. 1290, or bradford@salk.edu.

The study was funded by grants from the National Institutes of Health.

Scott Turner | Brown University
Further information:
http://www.brown.edu/Administration/News_Bureau/2002-03/02-068.html

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