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Metals and neurodegenerative diseases

- Role of copper and zinc in synaptic plasticity

- Manganese in parkinsonism

- Imaging and speciation of iron in dopamine neurons

- Speciation of copper and zinc in superoxide dismutase and amyotrophic lateral sclerosis

- Copper deficit, proteinopathy of superoxide dismutase and Parkinson’s disease

Nuclear Toxicology: toxic effects of elements used in nuclear industry and research

- Uranium neurotoxicology

- Cobalt oxide

Manganese in parkinsonism

Manganèse et parkinsonisme 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 (...)

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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 (...)

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Role of copper and zinc in synaptic plasticity

Rôle du cuivre et du zinc dans la plasticité synaptique 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 for (...)

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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 (...)

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Speciation of Cu and Zn in superoxide dismutase and amyotrophic lateral sclerosis

Spéciation du Cu et du Zn de 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 (...)

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Pulmonary toxicity of cobalt oxide particles : a Trojan-horse mechanism

In case of internal contamination in nuclear power plants, the isotope most frequently found among workers is 60Co from Co oxide particles. The lung is the critical organ, most of the time after exposure by inhalation of contaminated vapors. The purpose of this study conducted in collaboration with CEA teams within the frame of the Nuclear Toxicology Program (ToxNuc) was to describe the chemical mechanisms of cobalt toxicity either in soluble form or as oxide, on human lung cells. Cobalt (...)

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Imaging and speciation of iron 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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