Charakterisierung von Peroxiredoxin 2 im zentralen Nervensystem bei Multipler Sklerose

Characterization of peroxiredoxin 2 in the central nervous system in multiple sclerosis

by David Andreas Winkler née Voigt
Doctoral thesis
Date of Examination:2021-10-21
Date of issue:2021-10-21
Advisor:Prof. Dr. Wolfgang Brück
Referee:Prof. Dr. Wolfgang Brück
Referee:Prof. Dr. Michael Müller
Referee:Prof. Dr. Thomas Meyer
Persistent Address: http://dx.doi.org/10.53846/goediss-8882

 

 

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Abstract

English

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, characterized by demyelination and axonal damage as well as neuronal degeneration. Oxygen-derived free radicals are an important factor leading to tissue damage in inflammatory MS lesions. As an important scavenging enzyme family, peroxiredoxins (PRDXs) play a crucial role in preventing oxidative damage. Peroxiredoxine 2 (PRDX2), a member of this family, displays a particular high reaction rate with hydrogen peroxide as shown in various kinetic studies. In the present study the PRDX2 expression was examined in formalin-fixed, paraffin-embedded brain tissue from MS patients with long-standing, chronic disease as well as controls. PRDX2, investigated by immunohistochemistry, was found to be upregulated in chronic active white matter MS lesions mainly in astrocytes, and its expression level was positively correlated with the degree of inflammation (microglia/macrophage and T cell infiltration) and oxidative stress (determined by astrocytic NAD(P)H quinone dehydrogenase 1/NQO1 expression). In the grey matter, PRDX2 expression was found in neurons in leukocortical lesions. Additionally performed in-vitro experiments showed that oxidative stress alone leads to an enhanced NQO1 expression at the mRNA level in murine astrocytes. However, exposure to oxidative stress did not enhance PRDX2 expression. The same was observed in the neuroblastoma cell line SH SY5Y. Furthermore, the transcription of PRDX2 and NQO1 in murine astrocytes after incubation with IFN-γ, IL-1β, TNF-α, TGF-β1 or BDNF was unaltered. These data suggest that PRDX2 expression contributes to the resistance of astrocytes against oxidative damage in MS and its transcription is neither directly influenced by the presence of oxidative stress nor by the cytokines IFN-γ, IL-1β, TNF-α, TGF-β1 oder BDNF.
Keywords: multiple sclerosis (MS); oxidative stress; peroxiredoxin 2 (PRDX2); NAD(P)H quinone dehydrogenase 1 (NQO1)
 
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