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Exactly what has been discovered? In the June 26 issue of Science magazine, NIH researchers reported the precise identification of an abnormal gene responsible for some cases of Parkinson's disease (PD). The authors, including Dr Mihael Polymeropoulos at the National Human Genome Research Institute, discovered a tiny mistake in the gene that codes for a protein called alpha synuclein. While this protein is well known to neuroscientists, a relation to the cause of PD has not been previously suspected. Who is affected by this gene? The present report follows up on an earlier study by the same group which found that the parkinsonism affecting a large southern Italian family could be linked to a gene located on the long arm of chromosome 4. This family has rather typical PD both in relation to disease symptoms and neuropathological changes in the central nervous system. It differs in that the age of onset tends to be a little earlier and the subsequent rate of progression is somewhat faster. In this most recent paper, the same gene abnormality was also reported to occur in three parkinsonian families of Greek origin. Does this finding mean that there is a genetic basis for most or all cases of PD? PD affects more than a half-million Americans; every year some 50,000 new cases are discovered in this country alone. A few families like those reported here, have an autosomal dominant form of PD where - on average - half the children of a couple, one of whom has the gene abnormality, will come down with the disorder. But these families are relatively rare. For most individuals with PD there is no obvious genetic basis. Nevertheless, many scientists now think that a majority of parkinsonian cases reflect both genetic and environmental influences. The genetic component may act by increasing the vulnerability of dopamine-containing nerve cells for injury by some common, by itself relatively innocuous, environmental factor. How does the genetic abnormality cause nerve cell death? Much is already known about the protein synthesized as a result of instructions given by this abnormal gene. Synuclein is concentrated in or near vesicles that congregate at the terminals of many types of neurons found in the brain. Its normal function is not well understood and how the abnormality leads to neuronal degeneration remains to be determined. Since synuclein is not unique to dopamine-containing neurons, something in addition to the abnormal protein must be present to make these cells especially vulnerable. What new areas of research must now be conducted? Since not all PD is explained by this genetic abnormality, the search for other PD related genes must proceed. At the same time work can now begin on precisely how dopamine-containing neurons die in PD. Current evidence suggests that the neurodegenerative process involves a cell suicide mechanism called apoptosis. Many potential triggers for apoptosis are currently being investigated. Some involve the possibility that damage may result from an excessive generation of free radicals, although a number of other contributory factors have also been implicated. Ways to approach these lines of inquiry are fairly well established and with the discovery of the synuclein abnormality a much more focused effort can now begin. What is the relation of this gene abnormality to Alzheimer's disease? PD and AD have often been lumped together as rather similar neurodegenerative disorders. Scientists have felt that what is learned about one of these diseases may shed light on the other. AD is characterized neuropathologically by the presence of neuritic plaques. These plaques are mainly composed of a fibrillous material called beta-amyloid. Interestingly, the second most abundant plaque constituent is a small piece of normal synuclein. Whether the tight association between the synuclein derivative and beta-amyloid effects their neurotoxic potential remains to be established. What does this finding mean for the discovery of better treatments for PD? Some knowledge of the cause of a disease is an important prelude to the discovery of a cure. Unfortunately, going from an understanding of a disease mechanism to the development of a safe and effective treatment can be a long and arduous process. The good news is that we now have a much better handle on what to do in order to make more rapid progress. A lot of hard work plus a bit of good luck are still needed. Clearly, this wonderful discovery brings us much closer to the goal we all seek. If you have any questions about this information and would like more information about Parkinson's Disease and the National Parkinson Foundation, please call 1-800-327-4545, or visit our World Wide Web site: http://www.parkinson.org .