title: Blocking the phosphatidylinositol 3-kinase pathway inhibits neuregulin-1-mediated rescue of neurotoxicity induced by Aβ1-42.
abstract: OBJECTIVE
  Neuregulin-1 (NRG1) has an important role in both the development and the plasticity of the brain as well as neuroprotective properties. In this study, we investigated the downstream pathways of NRG1 signalling and their role in the prevention of Aβ1-42 -induced neurotoxicity.
  
  
  METHODS
  Lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) generation, superoxide dismutase (SOD) activity and TUNEL staining were assayed to examine the neuroprotective properties in primary rat cortical neurons.
  
  
  RESULTS
  The inhibition of PI3K/Akt activation abolished the ability of NRG1 to prevent Aβ1-42 -induced LDH release and increased TUNEL-positive cell count and reactive oxygen species accumulation in primary cortical neurons.
  
  
  CONCLUSIONS
  Our results demonstrate that NRG1 signalling exerts a neuroprotective effect against Aβ1-42 -induced neurotoxicity via activation of the PI3K/Akt pathway. Furthermore, this suggests that NRG1 has neuroprotective potential for the treatment of AD.
authors.affiliation: Department of Anatomy and Neuroscience, College of Medicine, Eulji University, Daejeon, Korea.
authors.forename: Tai-Kyoung
authors.initials: TK
authors.lastname: Baik
authors.affiliation: Department of Anatomy and Neuroscience, College of Medicine, Eulji University, Daejeon, Korea.
authors.forename: Young-Jung
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Neuroscience, College of Medicine, Eulji University, Daejeon, Korea.
authors.forename: Se-Mi
authors.initials: SM
authors.lastname: Kang
authors.affiliation: Department of Anatomy and Neuroscience, College of Medicine, Eulji University, Daejeon, Korea.
authors.forename: Dae-Yong
authors.initials: DY
authors.lastname: Song
authors.affiliation: Department of Physiology and Biophysics, College of Medicine, Eulji University, Daejeon, Korea.
authors.forename: Sun Seek
authors.initials: SS
authors.lastname: Min
authors.affiliation: Department of Anatomy and Neuroscience, College of Medicine, Eulji University, Daejeon, Korea.
authors.forename: Ran-Sook
authors.initials: RS
authors.lastname: Woo
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020890:Neuregulin-1 / Q000494:pharmacology* / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000378:metabolism* / Q000633:toxicity; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D020890:Neuregulin-1; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D058539:Phosphatidylinositol 3-Kinase
keywords: Alzheimer's disease; PI3K/Akt; amyloid beta-peptide; neuregulin 1; neurotoxicity