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

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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 locus coeruleus of PD patients. The results also showed that the levels of SOD1 are correlated with the amount of copper in brain, suggesting that a decrease of the copper concentration could compromise the mechanisms of defense against oxidative stress in brain area affected by PD.

Figure 1. Decrease of the copper concentration in subtantia nigra (SN) of PD cases. The measurements were performed by synchrotron radiation x-ray fluorescence microscopy (SRXFM) and particle induced x-ray emission (PIXE). Normal = control group, Parkinson = Parkinson’s disease, ILBD = Incidental Lewy Body disease, AD = Alzheimer’s disease (Neurobiology of Aging (2014), 35, 858-866).

As a result of these findings, we were also involved with the first demonstration of SOD1 aggegates in PD brain (Movement Disorders (2016), 31, S241-S242 et Acta Neuropathologica (2017), 134, 113-127). These aggregates are related to neuronal loss but are different from the well known apha-synucleine aggregates. Moreover, they resemble that of toxic SOD1 inclusions found in motor neurons of SOD1-associated cases of familial amyotrophic sclerosis. In PD cases, our measurements showed an increase of the electric point of SOD1 (i.e. a decrease of the net charge), a misfolded conformation and a copper deficiency in SOD1 aggregates. These data suggest a common mechanism for SOD1 aggregation and toxicity in these two neurodegenerative diseases.

Figure 2. a) Demonstration of SOD1 aggregates (white arrows) in substantia nigra pars compacta of Parkinson’s disease (PD) case. These aggregates are largely different from alpha-synucleine. Scale bar 20 µm.b) Increase of SOD1 pI in brain homogenates of PD cases compared to control cases (Acta Neuropathologica (2017), 134, 113-127).


Discipline of Biomedical Science and Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia

The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC 3052, Australia

Inserm, U836, Team 6, Rayonnement Synchrotron et Recherche Médicales, Grenoble Institut des Neurosciences, Grenoble, France


Amyotrophic lateral sclerosis-like superoxide dismutase 1 proteinopathy is associated with neuronal loss in Parkinson’s disease brain
Trist B.G., Davies K.M., Cottam V., Genoud S., Ortega R., Roudeau S., Carmona A., De Silva K., Wasinger V., Lewis S.J.G., Sachdev P., Smith B., Troakes C., Vance C., Shaw C., Al-Sarraj S., Ball H.J., Halliday G.M., Hare D.J., Double K.L. (2017), Acta Neuropathologica, 134, 113-127. [pubmed] [link]

Sod1 aggregation : A pathological link between Parkinson’s disease and amyotrophic lateral sclerosis ?
Trist B.G., Davies K.M., Genoud S., Smoothy V., Halliday G.M., Roudeau S., Carmona A., Perrin-Verdugier L., Ortega R., Double K.L. (2016), Movement Disorders, 31, S241-S242.

Copper pathology in vulnerable brain regions in Parkinson’s disease
Davies K.M., Bohic S., Carmona A., Ortega R., Cottam V., Hare D.J., Finberg J.P.M., Reyes S., Halliday G.M., Mercer J.F.B, Double K.L., (2014), Neurobiology of Aging, 35, 858-866. [pubmed] [link]