Insights into mammalian peroxiredoxins : expression in the central nervous system with a focus on neuronal populations affected in neurodegenerative disorders.

Peroxiredoxins (PRDXs or Prxs) are peroxidases able to reduce peroxides with a high efficiency, conferring to these enzymes functions in cytoprotection and redox signaling. PRDXs are abundant and widely expressed in most mammalian tissues. Recently, a modified pattern of PRDXs has been reported in neurodegenerative disorders such as Parkinson’s disease (PD), in term of expression level or post-translational modifications, with consequences for their activity. Emerging evidence point to the potential role of PRDXs in the pathogenesis of these neurodegenerative diseases. No systematic analysis of PRDX expression in the central nervous system (CNS) has been conducted so far. In this work, we first confirmed PRDX cell type expression in the mouse CNS by immunohistochemistry (IHC) through co-localization with specific markers such as NeuN, GFAP, Olig2 and Mac1. Several PRDXs are mainly expressed in glial cells (PRDX4 and PRDX6), but most of them are expressed in neurons (PRDX2 to PRDX5). Moreover, focusing on neuronal PRDXs, we report a complete characterization of PRDX expression levels in the most representative neuronal populations of the murine CNS with IHC procedures. Finally, tyrosine hydroxylase-PRDX double immunofluorescence showed that PRDX2 to PRDX5 are moderately to weakly expressed in the dopaminergic neurons from substantia nigra pars compacta, the neuronal population affected in PD. This faint expression could contribute to the vulnerability of these neurons in the disease. At the opposite, PRDXs are strongly expressed in motor neurons of the spinal cord which degenerate in the Amyotrophic Lateral Sclerosis (ALS). Further investigations will be needed to determine whether PRDXs play a major role in neurodegeneration