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IAPs are essential for GDNF-mediated neuroprotective effects in injured motor neurons in vivo

D Perrelet1, A Ferri, P Liston

  • 1Division Clinical Neuromuscular Research & Department APSIC, Faculty of Medicine, 1 rue Michel Servet, 1211 Geneva 4, Switzerland.

Nature Cell Biology
|January 29, 2002
PubMed

Insights

Inhibitors of apoptosis (IAP) proteins XIAP and NAIP are crucial for glial cell-derived neurotrophic factor (GDNF) to protect motor neurons. This discovery reveals key signaling pathways for neuroprotection.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Neuronal apoptosis is implicated in embryonic development and neurodegenerative diseases.
  • Inhibitors of apoptosis (IAP) proteins suppress apoptosis by inhibiting caspases.
  • The downstream targets of neurotrophic factors, like glial cell-derived neurotrophic factor (GDNF), remain largely unidentified.

Purpose of the Study:

  • To investigate the role of IAP proteins in the intracellular response to GDNF.
  • To identify downstream targets of GDNF signaling in motor neuron survival.

Main Methods:

  • Investigated the involvement of XIAP and NAIP in GDNF signaling.
  • Examined GDNF regulation of XIAP and NAIP levels in motor neurons post-sciatic nerve axotomy in newborn rats.
  • Assessed the impact of inhibiting XIAP or NAIP activity on GDNF-mediated neuroprotection.

Main Results:

  • XIAP and NAIP, but not HIAP2, were directly involved in the intracellular response to GDNF.
  • GDNF was found to regulate endogenous levels of XIAP and NAIP in motor neurons following sciatic nerve axotomy.
  • Inhibition of XIAP or NAIP activity abrogated the neuroprotective effects mediated by GDNF.

Conclusions:

  • XIAP and NAIP are essential components of GDNF's intracellular signaling pathway.
  • These findings highlight the critical role of XIAP and NAIP in GDNF-mediated motor neuron survival.

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