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Adult Neurogenesis

開催日 2014/9/12
時間 17:10 - 18:10
会場 Room J(313+314)
Chairperson(s) 影山 龍一郎 / Ryoichiro Kageyama (京都大学ウイルス研究所 / Institute for Virus Research, Kyoto University, Japan)
金子 奈穂子 / Naoko Kaneko (名古屋市立大学大学院医学研究科 再生医学分野 / Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Japan)

Ecto-domain phosphorylation of Nogo-66 receptor promotes neuronal cell production from adult neural stem cells

  • O2-J-5-2
  • 武井 義則 / Yoshinori Takei:1 
  • 1:京都大学 / Kyoto University, Japan 

The adult mammalian central nervous system (CNS) cannot be repaired spontaneously after injury, which is partly due to the myelin-associated proteins including Nogo-A, myelin-associated glycoprotein and oligodendrocyte myelin glycoprotein. Nogo-66 receptors (NgRs) are common receptors for those myelin-associated inhibitors of the regeneration, as well as for another group of regeneration inhibitors chondroitin sulphate proteoglycans. Inhibition of NgR activation can promote functional recovery of the spinal cord after traumatic injury. We previously reported that treatment of cells with protein kinase A (PKA) phosphorylated the ecto-domains of NgRs, which impedes the binding of the myelin-associated agonists (1). Here, we show that administration of PKA and ATP promotes recovery from spinal cord injury (2). NgR1 was expressed in neural stem/progenitor cells derived from the adult spinal cord. Inhibition of NgR1 enhanced neuronal cell production from the neural stem/progenitor cells, in vitro. Consistent with these results, administration of PKA and ATP phosphorylated NgR1 in the spinal cord in vivo and induced cells expressing markers for neuronal precursor cells, which is strictly inhibited without the treatment. Thus, inhibition of NgR1 in NSPs can promote neuronal cell production, which could contribute to the recovery of locomotor function from spinal cord injury.

(1) Takei, Y. Phosphorylation of nogo receptors suppresses nogo signaling, allowing neurite regeneration. Sci Signal 2, ra14 (2009).
(2) Suehiro K et al. Ecto-domain phosphorylation promotes functional recovery from spinal cord injury. Sci. Rep 4, SREP-13-04540, DOI: 10.1038/srep04972 (2014).

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