Roles for the pro-neurotrophin receptor sortilin in neuronal development, aging and brain injury.

Research output: Research - peer-reviewJournal article

  • Pernille Jansen
    Pernille JansenDenmark
  • Klaus Giehl
    Klaus GiehlDenmark
  • Jens R Nyengaard
  • Kenneth Teng
    Kenneth TengDenmark
  • Oleg Lioubinski
    Oleg LioubinskiDenmark
  • Susanne S Sjoegaard
    Susanne S SjoegaardDenmark
  • Tilman Breiderhoff
    Tilman BreiderhoffDenmark
  • Michael Gotthardt
    Michael GotthardtDenmark
  • Fuyu Lin
    Fuyu LinDenmark
  • Andreas Eilers
    Andreas EilersDenmark
  • Claus M Petersen
  • Gary R Lewin
    Gary R LewinDenmark
  • Barbara L Hempstead
    Barbara L HempsteadDenmark
  • Thomas E Willnow
    Thomas E WillnowDenmark
  • Anders Nykjaer
  • Department of Medical Biochemistry
  • Stereological Research Laboratory
  • Institute of Clinical Medicine
  • The Department of Pathology - ÅKH
Neurotrophins are essential for development and maintenance of the vertebrate nervous system. Paradoxically, although mature neurotrophins promote neuronal survival by binding to tropomyosin receptor kinases and p75 neurotrophin receptor (p75(NTR)), pro-neurotrophins induce apoptosis in cultured neurons by engaging sortilin and p75(NTR) in a death-signaling receptor complex. Substantial amounts of neurotrophins are secreted in pro-form in vivo, yet their physiological significance remains unclear. We generated a sortilin-deficient mouse to examine the contribution of the p75(NTR)/sortilin receptor complex to neuronal viability. In the developing retina, Sortilin 1 (Sort1)(-/-) mice showed reduced neuronal apoptosis that was indistinguishable from that observed in p75(NTR)-deficient (Ngfr(-/-)) mice. To our surprise, although sortilin deficiency did not affect developmentally regulated apoptosis of sympathetic neurons, it did prevent their age-dependent degeneration. Furthermore, in an injury protocol, lesioned corticospinal neurons in Sort1(-/-) mice were protected from death. Thus, the sortilin pathway has distinct roles in pro-neurotrophin-induced apoptotic signaling in pathological conditions, but also in specific stages of neuronal development and aging.
Udgivelsesdato: 2007-Nov
Original languageEnglish
JournalNature Neuroscience
Volume10
Issue number11
Pages (from-to)1449-57
Number of pages8
ISSN1097-6256
DOIs
StatePublished - 2007

    Research areas

  • Aging, Animals, Animals, Newborn, Apoptosis, Brain Injuries, Cell Count, Cells, Cultured, Embryo, Mammalian, Gene Expression Regulation, Developmental, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Nerve Tissue Proteins, Neurons, Receptors, Nerve Growth Factor, Retina, Signal Transduction, Superior Cervical Ganglion, Time Factors, Tyrosine 3-Monooxygenase

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