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Our Research
The PRC is dedicated to funding important projects centered around three very important questions:
What are the genetic causes of familial form of PD?
Understanding the cause(s) of PD is complicated by the fact that it appears to have both genetic and environmental causes. A few rare forms of familial PD are caused by single gene mutations. Several have been identified and there are ongoing efforts to identify additional genes. While all forms of familial PD are uncommon, identification is important since it provides insight into how dopamine neurons ultimately die, even with non-familial cases.
The PRC scientists have made the exciting discovery of a new locus for familial PD. They are currently working with a French-Canadian family to identify the exact gene located at this locus linked to PD. They have collected blood samples from 65 individuals from this large Parkinson's family where 14 have been affected with Parkinson's. When the identification of this new gene is made, this knowledge will provide important clues into how PD is initiated and progresses in patients.
Are there susceptibility genes which may contribute to idiopathic PD?
While the identification of familial PD genes is important, the vast majority of PD patients do not have a simple direct link to one gene. In this regard, it is likely that there is a complex series of susceptibility genes, which might predispose individuals to PD with an appropriate (and unfortunate) environmental insult. These genes likely influence how dopamine neurons function. Therefore, fundamental efforts must be made to not only identify these susceptibility genes, but to also identify potential environmental insults.
The PRC scientists are addressing this important question by setting up a sophisticated biological screening system using more simple animals (worms and fish) to identify which genes might make one more susceptible to dopamine neuron loss. By harnessing the power of genetic screens only possible in these lower animals, we can identify genes that are potentially critical for dopaminergic function. Once identified, we can then assess how these genes may potentially make individuals more susceptible to PD.
How do these genes control how dopamine neurons die in PD?
Once factors are identified as described above, it is critical to then understand the mechanisms by which these genes cause death. Several genes that provide a direct link to PD have already been identified. These include recently identified PD genes, DJ-1, PINK1 and LRRK2. How these genes actually cause PD is unknown. The scientists of the PRC have expertise in a wide variety of model animal systems to study these genes in dopamine neuron loss. These systems include the well known mouse system. However, the PRC scientists can also examine these genes in a manner that cannot be readily performed in mice. By using a variety of simpler and surprisingly elegant animal systems including the drosophila fruitfly, the zebra fish, and the C. elegans worm, we can more quickly unravel the mysteries of how these genes provoke the onset of PD. The scientists, by use of a wide variety of genetic and biochemical approaches are dedicated to understanding how these genes may lead to PD.
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