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Human Diseases and the role of Molecular and Cellular Stress
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| Project : Identification of Genes as Risk Factors for Parkinson’s Disease |
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Parkinson's disease (PD) is a progressive neurological movement disorder involving the loss of dopamine producing neurons and is the second most common neurodegenerative disorder that affects over 50,000 Australians. There is a critical need for an effective treatment of Parkinson's disease, since current therapies (L-DOPA) are only partially effective in treating some symptoms and do not stop the progression of the disease nor replace lost motor neurons.
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The protein a-synuclein is central to the development of PD as it can oligomerise and or aggregate and is the principal component of Lewy Bodies, the hallmark pathological protein inclusions in PD. Mutations in the a-synuclein gene or a 50% increase in expression of wild-type a-synuclein results in PD and we have identified that mutant or elevated a-synuclein interferes with a critical protein trafficking step. However the vast majority of PD cases do not involve mutations in the coding sequence of a-synuclein but likely result from a complex interaction of unknown predisposing genes (risk factors) and environmental influences. These factors are very likely to impact the propensity of normal levels of wild-type a-synuclein to aggregate and/or induce a trafficking defect.
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This project employs a custom constructed whole genomic approach to identify these PD risk factor genes. These genes will then be investigated using a broad array of genetic, cell and molecular approaches to both confirm their association with PD and identify the underlying molecular mechanism(s) responsible for contributing to PD. Identifying inherited risk factors will enhance our understanding of how Parkinson's disease develops and is an important step towards preventing the disease or to develop therapeutic agents that may inhibit the degeneration of neurons.
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