Animal models of amyotrophic lateral sclerosis : are peroxiredoxins involved in the pathogenesis of the disease ?
(2017)
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- Authors
- Supervisors
- Knoops, Bernard
- Abstract
- ALS is a neurodegenerative disorder characterized by death of motor neurons and progressive paralysis. A growing body of evidence suggests a potential implication of peroxiredoxins (Prdxs), ubiquitously expressed peroxidases, in this pathology. The role of astrocytes in neuronal survival is actively debated in the literature. In this study, dramatic induction of the expression of the six isoforms of Prdxs in reactive astrocytes was revealed both in vivo and in vitro. The role of Prdx5 and mitochondrial Prdx3 in ALS seems to be of particular interest as we have shown that these two Prdxs were specifically induced in reactive hSOD1G93A-expressing astrocytes in vitro. Moreover, the presence of Prdx3 and Prdx5 in hSOD1G93A-containing aggregates suggests that these Prdxs could be involved in this neurotoxic phenomenon. In addition to their antioxidant activity, the implication of Prdxs in neuro-inflammation seems to be of particular interest. Data provided by our work highlighted the importance of IL1-β and IFN-γ in the regulation of several Prdxs in vitro. Finally, the inactivation of Prdx5 expression in double transgenic animals brought an important piece of information on the potential role of this protein in the etiology of ALS. Contrarily to our initial hypothesis, the lack of Prdx5 expression was associated with the improvement of animal condition on the pre- and early symptomatic stages of the disease. However, micro-array analyses of spinal cord lysates from Prdx5gt/gt/SOD1G93A mice at the advanced stages of the disease have revealed that Prdx5 inactivation was correlated with the downregulation of a series of molecular chaperones and the upregulation of pathways involved in neuro-inflammation. Altogether, these data link Prdx5 to the glial neurotoxicity in ALS context.
- Affiliations
Citations
Kuznetsova, O. (2017). Animal models of amyotrophic lateral sclerosis : are peroxiredoxins involved in the pathogenesis of the disease ? https://hdl.handle.net/2078.5/180100