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Metals and neurodegenerative diseases

-  role of copper and zinc in synaptic plasticity

- Imaging and speciation of manganese in dopamine neurons

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

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

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

- cobalt oxide

- uranium

Role of copper and zinc in synaptic plasticity

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 the stability of the cytoskeleton of F-actin and (...)

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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 and manganese 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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