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Parkinson's Disease and Movement Disorders

Molecular mechanisms of the movement disorders

We are searching for genes involved in Parkinson’s disease (PD) and other movement disorders, to provide clues for understanding of the disease mechanisms, and to identify novel targets for the development of therapies to stop and prevent these diseases. 

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PD is a common degenerative disease of the brain characterized by the progressive loss of dopaminergic neurons and the formation of neuronal inclusions (Lewy bodies) in the surviving neurons. The pathogenesis of PD remains mostly unknown, but a growing list of gene defects identified in the past few years in some inherited forms of the disease offers unprecedented, exciting opportunities to disentangle the complex molecular pathways leading to PD.

Gene finding

My group uses a number of unbiased strategies for the identification of novel genes causing or predisposing to PD and other movement disorders, such as dystonias, paroxysmal dyskinesias, Tourette syndrome, and restless legs syndrome.

Our experimental approaches include family-based linkage mapping, homozygosity mapping, positional cloning, next-generation sequencing technologies (exome sequencing and whole genome sequencing), and tools for insilico analysis of DNA and protein sequence data.

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Functional studies

Each of the Mendelian forms of disease might provide important clues for understanding of the pathogenesis also in the more common, complex forms of the disease.
Mutations in the FBXO7 gene cause PARK15, a recently recognized form of juvenile parkinsonism.
Our group is using cell-based in vitro approaches, and the zebrafish as a model organism to investigate the normal function of the protein encoded by the FBXO7 gene, and of the mechanisms of neuronal cell death caused by its dysfunction.

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Genotype-phenotype correlations

We are also interested in studying known disease-causing genes (for example, the PD-causing genes SNCA, LRRK2, VPS35, GBA, PRKN, PINK1, DJ-1, ATP13A2, PLA2G6, FBXO7) in large series of patients, to characterize the associated genotypic and phenotypic spectra, and to investigate genotype-phenotype correlations.

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Our laboratory research relies on the dedication and the excellent investigations performed by a network of collaborators (mostly neurologists) operating in several countries, including The Netherlands, Italy, Portugal, Spain, United Kingdom, Brazil, Taiwan, Zambia, United States, and other countries, for the study of large families with Mendelian neurodegenerative disease, other movement disorders, as well as case-control series, and genetically isolated populations. We are currently conducting research on the genetics of PD in Sardinia, a Mediterranean genetic isolate.