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Christophe Lo Bianco"Development of new genetic models and therapeutic approaches for neurodegenerative diseases"

Abstract :


Although several genes have been associated with familial Parkinson´s disease (PD), the etiology of sporadic PD, the most common form (95% of PD cases), is still unknown.
Considerable evidences suggest a multifactorial etiology involving both genetic susceptibility factors and environmental exposures. Mutations in the glucocerebrosidase (GBA) gene were recently described to be a susceptibility factor for developing sporadic PD and also dementia with Lewy bodies (DLB). Interestingly, homozygous mutations in the GBA gene cause the glycosphingolipidstorage Gaucher’s Disease (GD),resulting from a GBA enzyme deficiency. Major efforts are devoted to investigate the function of GBA, either in the whole CNS, in specific neuronal populations or in non-neuronal cells as microglia cells. As aging is the major risk factor of PD and other degenerative diseases, we are seeking to elucidate the role of aging, especially mitochondrial DNA mutations (mtDNA), in PD. This research should lead to a better understanding of the mechanism leading to cell death in neurodegenerative disorders. We are also generating genetic mouse models of both sporadic PD and neuronopathic GD. By combining genetic, behavioral, molecular and cellular biological approaches, we are seeking to understand the role of risk factors in neurodegenerative disorders, to dissect the mechanism of cellular degeneration and how each cell type (neuron versus glial cells) contributes to the neuropathology. For these purposes, we are developing new and crucial genetic tools to modulate the expression of genes in vivo using either transgenic animals (full and conditional knockout) or viral vectors to express or shut down a specific gene in a targeted brain region.

Selected publications

Lo Bianco, C*, Enquist*IB, Ooka A , Kirik D., Björklund A., and Karlsson S.
Murine models of Gaucher´s disease. Proc Natl Acad Sci U S A, 2007 Oct 30;104(44):17483-8. *Equal contribution and co-authorship
Lo Bianco, C., Schneider, B. L., Bauer, M., Sajadi, A., Brice, A., Iwatsubo, T. & Aebischer, P. (2004). Lentiviral vector delivery of parkin prevents dopaminergic degeneration in an a-synuclein rat model of Parkinson’s disease.
Proc Natl Acad Sci U S A, 101(50):17510-5

Lo Bianco, C., Deglon, N., Pralong, W. & Aebischer, P. (2004) Lentiviral nigral delivery of GDNF does not prevent neurodegeneration in a genetic rat model of Parkinson's disease. Neurobiology of Disease, 17(2):283/9.
Lo Bianco, C., Ridet, J. L., Schneider, B. L., Deglon, N. & Aebischer, P. (2002) a -Synucleinopathy and selective dopaminergic neuron loss in a rat lentiviral-based model of Parkinson's disease. Proc Natl Acad Sci U S A 99, 10813-8.

Christophe Mulle