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Jens Randel Nyengaard

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

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  • Pernille Jansen, Denmark
  • Klaus Giehl, Denmark
  • Jens R Nyengaard
  • Kenneth Teng, Denmark
  • Oleg Lioubinski, Denmark
  • Susanne S Sjoegaard, Denmark
  • Tilman Breiderhoff, Denmark
  • Michael Gotthardt, Denmark
  • Fuyu Lin, Denmark
  • Andreas Eilers, Denmark
  • Claus M Petersen
  • Gary R Lewin, Denmark
  • Barbara L Hempstead, Denmark
  • Thomas E Willnow, Denmark
  • 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
Pages (from-to)1449-57
Number of pages8
Publication statusPublished - 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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