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dc.contributor.authorCollins, SJ
dc.contributor.authorTumpach, C
dc.contributor.authorGroveman, BR
dc.contributor.authorDrew, SC
dc.contributor.authorHaigh, CL
dc.date.accessioned2020-12-17T03:05:08Z
dc.date.available2020-12-17T03:05:08Z
dc.date.issued2018-09-01
dc.identifierpii: 10.1007/s00018-018-2790-3
dc.identifier.citationCollins, S. J., Tumpach, C., Groveman, B. R., Drew, S. C. & Haigh, C. L. (2018). Prion protein cleavage fragments regulate adult neural stem cell quiescence through redox modulation of mitochondrial fission and SOD2 expression. CELLULAR AND MOLECULAR LIFE SCIENCES, 75 (17), pp.3231-3249. https://doi.org/10.1007/s00018-018-2790-3.
dc.identifier.issn1420-682X
dc.identifier.urihttp://hdl.handle.net/11343/254737
dc.description.abstractNeurogenesis continues in the post-developmental brain throughout life. The ability to stimulate the production of new neurones requires both quiescent and actively proliferating pools of neural stem cells (NSCs). Actively proliferating NSCs ensure that neurogenic demand can be met, whilst the quiescent pool makes certain NSC reserves do not become depleted. The processes preserving the NSC quiescent pool are only just beginning to be defined. Herein, we identify a switch between NSC proliferation and quiescence through changing intracellular redox signalling. We show that N-terminal post-translational cleavage products of the prion protein (PrP) induce a quiescent state, halting NSC cellular growth, migration, and neurite outgrowth. Quiescence is initiated by the PrP cleavage products through reducing intracellular levels of reactive oxygen species. First, inhibition of redox signalling results in increased mitochondrial fission, which rapidly signals quiescence. Thereafter, quiescence is maintained through downstream increases in the expression and activity of superoxide dismutase-2 that reduces mitochondrial superoxide. We further observe that PrP is predominantly cleaved in quiescent NSCs indicating a homeostatic role for this cascade. Our findings provide new insight into the regulation of NSC quiescence, which potentially could influence brain health throughout adult life.
dc.languageEnglish
dc.publisherSPRINGER BASEL AG
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titlePrion protein cleavage fragments regulate adult neural stem cell quiescence through redox modulation of mitochondrial fission and SOD2 expression
dc.typeJournal Article
dc.identifier.doi10.1007/s00018-018-2790-3
melbourne.affiliation.departmentMedicine (RMH)
melbourne.affiliation.departmentInfectious Diseases
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleCellular and Molecular Life Sciences
melbourne.source.volume75
melbourne.source.issue17
melbourne.source.pages3231-3249
melbourne.identifier.nhmrc1105784
dc.rights.licenseCC BY
melbourne.elementsid1318675
melbourne.contributor.authorDrew, Simon
melbourne.contributor.authorCollins, Steven
melbourne.contributor.authorHaigh, Cathryn
melbourne.contributor.authorTumpach, Carolin
dc.identifier.eissn1420-9071
melbourne.identifier.fundernameidNHMRC, 1105784
melbourne.accessrightsOpen Access


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