Molecular pathophysiology of Parkinson's disease

PhD, Team Leader, PI, INSERM

Pr (PU-PH, MD, PhD), Team Leader, PI, AP-HP

Team presentation

The team "Molecular Physiopathology of Parkinson’s Disease" is interested in the complexity of Parkinson’s disease and conducts multidisciplinary research projects combining clinical evaluation, neuronal biology and genetics.

The 3 main goals of the Molecular Physiopathology of Parkinson’s Disease team are:

Identify new genetic factors of disease, such as genes responsible for familial forms, genes modifying progression or response to treatments, or non-coding elements of the genome affecting the biology of neurons.
To characterize molecular mechanisms responsible for disease, particularly those linked to PINK1 and Parkin dysfunction, and to study their effects on neuronal and immune cell biology.
Develop new clinical-genetic strategies for personalized prediction medicine.

Main publications

Lesage S, Lunati A, Houot M, Romdhan SB, Clot F, Tesson C, Mangone G, Toullec BL, Courtin T, Larcher K, et al., French Parkinson disease Genetics Study Group (PDG). Characterization of recessive Parkinson’s disease in a large multicenter study. Ann Neurol. 2020.

Jacoupy M, Hamon-Keromen E, Ordureau A, Erpapazoglou Z, Coge F, Corvol JC, Nosjean O, Mannoury la Cour C, Millan MJ, et al., The PINK1 kinase-driven ubiquitin ligase Parkin promotes mitochondrial protein import through the presequence pathway in living cells. Sci Rep. 2019, 9(1):11829.

Gendron J, Colace-Sauty C, Beaume N, Cartonnet H, Guegan J, Ulveling D, Pardanaud-Glavieux C, Moszer I, Cheval H, Ravassard P. Long non-coding RNA repertoire and open chromatin regions constitute midbrain dopaminergic neuron-specific molecular signatures. Sci Rep 2019, 9(1):1409.

Mouton-Liger F, Rosazza T, Sepulveda-Diaz J, Ieang A, Hassoun SM, Claire E, Mangone G, Brice A, Michel PP, Corvol JC, Corti O. Parkin deficiency modulates NLRP3 inflammasome activation by attenuating an A20-dependent negative feedback loop. Glia 2018, 66(8):1736-1751.

Corvol JC, Artaud F, Cormier-Dequaire F, Rascol O, Durif F, Derkinderen P, Marques AR, Bourdain F, Brandel JP, Pico F, et al., for the DIGPD study group. Longitudinal analysis of impulse control disorders in Parkinson’s disease. Neurology 2018, 91(3):e189-e20

Tesson C, Brefel-Courbon C, Corvol JC, Lesage S, Brice A; French Parkinson’s Disease Genetics Study Group. LRP10 in alpha-synucleiopathies. Lancet Neurol (Letter) 2018, 17(12):1034.

Cormier-Dequaire F., Bekadar S., Anheim M., Lebbah S., Pelissolo A., Krack P., Lacomblez L., Lhommée E., Castroto A., Azulay J.P., , BADGE-PD study group. Suggestive association between OPRM1 and impulse control disorders in Parkinson’s disease. Mov Disord 2018, 33(12):1878-1886.

Gautier CA, Erpapazoglou Z, Mouton-Liger F, Muriel MP, Cormier F, Bigou S, Duffaure S, Girard M, Foret B, Iannielli A, et al. The endoplasmic reticulummitochondria interface is perturbed in PARK2 knockout mice and patients with PARK2 mutations. Hum Mol Genet. 2016, 25(14):2972-2984.

Lesage S., Drouet V., Majounie E., Deramecourt V., Jacoupy M., Nicolas A., Cormier- Dequaire F., Hassoun S. M., Pujol C., et al., Loss of VPS1 3C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy. Am J Hum Genet 2016, 98(3), 500-513.

Bertolin G., Fournier M., Traver S., Ferrando-Miguel R., Saint Georges T., Grenier K. Ardila-Osorio H., Muriel M. P., Takahashi H., Lees A.J., et al., Gautier C., Guedin D., Parkin maintains mitochondrial levels of the protective Parkinson’s disease-related enzyme 17-beta hydroxysteroid dehydrogenase type 10. Cell Death Differ 2015, 22(10), 1563-1576.