Partenaires



CNRS Université Bordeaux
CNRS

Accueil du site > ANGLAIS > Research > CIS - Chemical Imaging and Speciation > Research projects > Iron and alpha-synuclein in dopamine neurons


Iron and alpha-synuclein in dopamine neurons

PNG - 575 bytes

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 hypothesis that iron content and distribution may be altered in cells over-expressing α-synuclein.

Using nano-SXRF and micro-PIXE chemical imaging methods, we quantified and described the distribution of iron at the subcellular level. We show that, in neurons exposed to an excess of iron, the overexpression of human α-synuclein leads to the increase of the level of intracellular iron and its redistribution in the cytoplasm, to the perinuclear region in the inclusions of α-synuclein (Figure 1).

Reproducible results were obtained on two different recombinant expression systems, on the rat midbrain primary neurons and on a rat neuroblastic cell line (PC12), infected with viral vectors expressing human α-synuclein. Our results link two specific molecular features of Parkinson’s disease, α-synuclein accumulation, and increased iron levels in substantia nigra (Ortega et al., 2016).

Figure 1. Nano-SXRF imaging of dopaminergic neurons exposed in vitro to excess iron without (higher panel) or with (lower panel) overexpression of alpha synuclein. In neurons over-expressing alpha-synuclein, iron accumulates in perinuclear inclusions rich in alpha-synuclein.

References

α-Synuclein over-expression induces increased iron accumulation and redistribution in iron-exposed neurons
Ortega R., Carmona A., Roudeau S., Perrin L., Dučić T., Carboni E., Bohic S., Cloetens P., Lingor P. (2016), Molecular Neurobiology, 53, 1925-1934. [pubmed] [link]