Neuregulin 1 Reduces Motoneuron Cell Death and Promotes Neurite Growth in an in Vitro Model of Motoneuron Degeneration

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder with no effective treatment currently available. The mechanisms of motoneuron (MN) death are still unclear, but glutamate excitotoxicity and neuroinflammatory reaction are two main features in the neurodegenerative process of ALS. Neuregulin 1 (NRG1) is a trophic factor highly expressed in MNs and neuromuscular junctions. This study used an in vitro model of spinal cord organotypic cultures (SCOCs) subject to chronic excitotoxicity to characterize the effect of NRG1 on MN survival. The results show that NRG1 increased MN survival through activation of ErbB receptors, reduced microglial reactivity, activated the pro-survival PI3K/AKT pathway, restored autophagic flux, and promoted motor and sensory neurite outgrowth.

• 1
  Addition of recombinant human NRG1 (rhNRG1) to spinal cord organotypic cultures (SCOCs) significantly increased motoneuron (MN) survival under chronic excitotoxicity.
• 2
  rhNRG1 activates ErbB receptors to promote motoneuron survival, as the neuroprotective effect was abolished by lapatinib (LP), an ErbB inhibitor.
• 3
  rhNRG1 reduces microglial reactivity and enhances motor and sensory neurite outgrowth in vitro.