Journal article

The prion protein regulates beta-amyloid-mediated self-renewal of neural stem cells in vitro

Steven J Collins, Carolin Tumpach, Qiao-Xin Li, Victoria Lewis, Timothy M Ryan, Blaine Roberts, Simon C Drew, Victoria A Lawson, Cathryn L Haigh



The beta-amyloid (Aβ) peptide and the Aβ-oligomer receptor, prion protein (PrP), both influence neurogenesis. Using in vitro murine neural stem cells (NSCs), we investigated whether Aβ and PrP interact to modify neurogenesis. Aβ imparted PrP-dependent changes on NSC self-renewal, with PrP-ablated and wild-type NSCs displaying increased and decreased cell growth, respectively. In contrast, differentiation of Aβ-treated NSCs into mature cells was unaffected by PrP expression. Such marked PrP-dependent differences in NSC growth responses to Aβ provides further evidence of biologically significant interactions between these two factors and an important new insight into regulation of NSC self-ren..

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Awarded by NHMRC

Awarded by ARC Future Fellowship

Awarded by Australian Research Council

Funding Acknowledgements

The authors would like to acknowledge Professor Colin Masters for his ongoing support and thank Dr Theo Mantamadiotis and Ms Gulay Filiz for their assistance with the cell cycle flow cytometry. This work was supported by an NHMRC program grant (#628946) and the Victorian Government's Operational Infrastructure Support program. SJC is supported by an NHMRC Practitioner Fellowship (#APP100581), SCD by an ARC Future Fellowship (FT110100199) and TMR by an Alzheimer's Australia fellowship.