title: Neuroprotective effect of melatonin on soluble Aβ1-42-induced cortical neurodegeneration via Reelin-Dab1 signaling pathway.
abstract: OBJECTIVE
  Soluble Aβ1-42oligomers play a vital role in the development and pathogenesis of Alzheimer's disease (AD). Melatonin could delay the progress of AD through multiple mechanisms. Reelin-Dab1 signaling plays an important role in AD, including neuronal function and synaptic plasticity. However, whether melatonin could exert its neuroprotective function against soluble Aβ1-42-induced neurotoxicity during AD development through regulating Reelin-Dab1 signaling remains poorly understood.
  
  
  METHODS
  AD rat model was established by soluble Aβ1-42repeated intracerebroventricular injection. Using immunohistochemistry and Western blot analyses, the effect of melatonin on synaptic plasticity, neuritic degeneration, and astrocyte activation was investigated in cerebral cortex. Meanwhile, the expression of Reelin and Dab1 was also examined in cerebral cortex. In our in vitro study, Reelin-Dab1 signaling was inhibited by Reelin antibody, and neuroprotective effect of melatonin against Aβ1-42was further determined.
  
  
  RESULTS
  Melatonin ameliorated the neurotoxiciy and astrocyte activation induced by Aβ1-42in the cerebral cortex. Melatonin also blocked the reduction in Reelin and Dab1 expression induced by Aβ1-42. Using in vitro study, Reelin inactivation completely abolished the protective effect of melatonin against Aβ1-42-induced neurotoxicity.
  
  
  CONCLUSIONS
  Melatonin might play its neuroprotective role against Aβ1-42through mediating Reelin-Dab1 signaling pathway. Melatonin could be a safe and remarkable therapeutic candidate for AD and other aged-associated neurodegenerative diseases.
authors.affiliation: a Department of Neurobiology and Key Laboratory of Neurodegenerative Diseases of Liaoning Province , Jinzhou Medical University , Jinzhou , P.R. China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Hu
authors.affiliation: a Department of Neurobiology and Key Laboratory of Neurodegenerative Diseases of Liaoning Province , Jinzhou Medical University , Jinzhou , P.R. China.
authors.forename: Pan
authors.initials: P
authors.lastname: Wang
authors.affiliation: a Department of Neurobiology and Key Laboratory of Neurodegenerative Diseases of Liaoning Province , Jinzhou Medical University , Jinzhou , P.R. China.
authors.forename: Shuman
authors.initials: S
authors.lastname: Zhang
authors.affiliation: a Department of Neurobiology and Key Laboratory of Neurodegenerative Diseases of Liaoning Province , Jinzhou Medical University , Jinzhou , P.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Ren
authors.affiliation: a Department of Neurobiology and Key Laboratory of Neurodegenerative Diseases of Liaoning Province , Jinzhou Medical University , Jinzhou , P.R. China.
authors.forename: Yiheng
authors.initials: Y
authors.lastname: Lv
authors.affiliation: a Department of Neurobiology and Key Laboratory of Neurodegenerative Diseases of Liaoning Province , Jinzhou Medical University , Jinzhou , P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yin
authors.affiliation: a Department of Neurobiology and Key Laboratory of Neurodegenerative Diseases of Liaoning Province , Jinzhou Medical University , Jinzhou , P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Bi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015816:Cell Adhesion Molecules, Neuronal / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016229:Amyloid beta-Peptides; D015816:Cell Adhesion Molecules, Neuronal; C499786:Dab1 protein, rat; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D000091042:Reelin Protein; C000717129:Reln protein, rat; C075222:amyloid beta-protein (1-42); C000717127:RELN protein, human; D012697:Serine Endopeptidases; D008550:Melatonin
keywords: Dab1; Melatonin; Reelin; neurodegeneration; soluble Aβ1–42