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Research projects
Role of copper and zinc in synapse formation
Iron and alpha-synuclein in dopamine neurons
Copper and zinc in superoxide dismutase and amyotrophic lateral sclerosis
Copper deficit, proteinopathy of superoxide dismutase and Parkinson’s disease
Manganese neurotoxicology
Neurotoxicologie du manganèse Manganese (Mn) is an essential metal but it is neurotoxic at high dose, leading to parkinsonism, a clinical syndrome with symptoms of Parkinson’s disease. We studied this toxicity in the case of a familial mutation affecting the Mn transporter SLC30A10. This protein is normally responsible for the efflux of Mn and protects the cell against the toxicity of this metal. Using organelle fluorescence optical microscopy and synchrotron X-ray fluorescence imaging, we (...)
Uranium neurotoxicology
Neurotoxicologie de l’uranium The main objective of this study was to describe the mechanisms of toxicity of natural uranium, after a continuous exposure of 7 days, on human SH-SY5Y cells presenting a dopaminergic phenotype. Cell viability was assessed for the first time on this cell type, showing that the cytotoxicity of uranium only occurred at high concentrations (> 125 μM), far above the expected values for uranium in the blood, even after occupational or accidental exposure. The SH-SY5Y (...)
Role of copper and zinc in synapse formation
Rôle du cuivre et du zinc dans la formation des synapses Thanks to an unprecedented spatial resolution (30 nm) achieved on the nanoimaging beamline ID16A at the ESRF we have described for the first time the distribution of biological metals at the synapse level, in the dendritic spines of glutamatergic neurons in culture. The results indicate a new role of copper and zinc in neuronal plasticity (Perrin et al., 2017). We have thus revealed the essential character of these biological metals (...)
Copper deficit, proteinopathy of superoxide dismutase and Parkinson’s disease
Déficit en cuivre, protéinopathie de la superoxyde dismutase et maladie de Parkinson We also study the role of copper in Parkinson’s disease (PD) in the frame of a collaboration with the team of Kay Double (University of Melbourne) and Dominic Hare (University of Melbourne). These studies demonstrated an alteration of the copper homeostasis in PD (Neurobiology of Aging (2014), 35, 858-866). The amount of copper and its transporter Ctr1 are indeed lowered in brains regions substantia nigra and (...)
Cu and Zn in superoxide dismutase and amyotrophic lateral sclerosis
Cu et du Zn dans la superoxyde dismutase et sclérose latérale amyotrophique Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motor neurons. The disease is rapidly progressive with a mean survival of three to five years because of the lack of effective therapy. The underlying causes are still elusive but the mechanisms are multifactorial. Several genes have been associated with ALS, the first of which is the gene coding the copper zinc (...)
Iron and alpha-synuclein in dopamine neurons
Disturbance of Fe homeostasis may play a crucial role in the pathogenesis of Parkinson’s disease by induction of oxidative stress and/or promotion of alpha-synuclein aggregation. Thus, Parkinson’s disease represents the most common α-synucleinopathy and iron levels are greater in the substantia nigra of patients with Parkinson’s disease, but the potential interconnection between these two molecular changes is still poorly understood. Since α-synuclein can bind iron in vitro we have tested the (...)
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