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Article Dans Une Revue Journal of Biological Chemistry Année : 2008

Prions impair bioaminergic functions through serotonin- or catecholamine-derived neurotoxins in neuronal cells

Résumé

The conversion of the cellular prion protein, PrPC, to an abnormal isoform, PrPSc, is a central event leading to neurodegeneration in prion diseases. Deciphering the molecular and cellular changes imparted by PrPSc accumulation remains an arduous task due to the small number of cell lines supporting prion replication. Here we introduce the 1C11 cell line as a new in vitro model to investigate prion pathogenesis. This cell line is a committed neuroectodermal progenitor able to differentiate into fully functional serotonergic or catecholaminergic neurons. 1C11 cells, which naturally express PrPC from the undifferentiated state, can be chronically infected with various prion strains. Prion infection does not promote any noticeable phenotypic change in the progenitor cells nor prevent the onset of the serotonergic and catecholaminergic differentiation programs. Pathogenic prions, however, deviate the overall neurotransmitter-metabolism in both pathways by decreasing bioamine synthesis, storage, and transport, and enhancing catabolism. Noteworthy, oxidized derivatives of both serotonin and catecholamines are selectively detected in the differentiated progenies of infected cells and contribute to irreversible impairment in bioamine synthesis. Finally, the level of PrPSc accumulation, that of infectivity, and the extent of all prion-induced changes in infected cells appear to be correlated. The report of such specific effects of infection on neuronal functions provides a foundation for dissecting the events underlying loss of neuronal homeostasis in prion diseases.
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hal-02666187 , version 1 (31-05-2020)

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Sophie Mouillet-Richard, Noriyuki Nishida, Elodie Pradines, Hubert H. Laude, Benoît Schneider, et al.. Prions impair bioaminergic functions through serotonin- or catecholamine-derived neurotoxins in neuronal cells. Journal of Biological Chemistry, 2008, 283 (35), pp.23782-23790. ⟨10.1074/jbc.M802433200⟩. ⟨hal-02666187⟩
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