A Fly Model for Parkinson's Disease

Researchers have genetically engineered strains of fruit flies to mimic many of the same symptoms as humans with Parkinson's disease. Researchers hope the insects, which suffer the premature death of certain neurons and can't climb walls as well as their normal counterparts, will help them learn what goes wrong in the brains of Parkinson's patients.

Scientists have debated for years whether genetics or some environmental trigger causes Parkinson's disease. In 1997, Mihael Polymeropoulos of the National Human Genome Research Institute in Bethesda, Maryland, and his colleagues found the first clear genetic link to the disease: Members of an Italian family that suffer from an early onset form of Parkinson's carry a mutation in a gene called a-synuclein (ScienceNOW, 26 June 1997). Researchers cautioned that a-synuclein was unlikely to explain most cases of the disease, but they hoped that animals that expressed the protein might help them uncover related causes. Last month, researchers announced that mice that carried extra copies of the human a-synuclein gene do indeed suffer neuron damage and develop motor problems in adulthood (Science, 18 February, p. 1265). The team is not certain whether it is the extra copies, or some property of the human protein, that causes the damage.

Now, neuroscientist Mel Feany and biochemist Welcome Bender of Harvard Medical School in Boston have created several strains of transgenic fruit flies that express different versions of the human a-synuclein gene. One strain produces the normal protein, while the other two produce mutant strains. In all three strains, the dopamine-producing neurons--the same ones that die in human Parkinson's disease--die off in adult flies, the pair reports in tomorrow's Nature. In addition, the neurons form so-called Lewy bodies, abnormal accumulations of protein that include high levels of the a-synuclein protein. Finally, the flies lose their ability to climb the wall of a test tube earlier in life than normal flies.

The symptoms support the idea that a-synuclein plays a key role in the development of the disease, says neuroscientist Leonard Muchy of the University of California, San Francisco, who helped to develop the a-synuclein mouse. "It is absolutely striking that species as diverse as flies and mice respond to the buildup of a-synuclein in such similar ways," he says. Feany agrees. The key advantage of the flies as a model, she notes, is that they're easy to produce. Additional mutants, combined with the information from the fly's newly completed genome, should help scientists pinpoint other proteins that play a role in the disease, she says.