title: N-Stearoyltyrosine protects primary cortical neurons against Aβ(1-40)-induced injury through inhibiting endocannabinoid degradation.
abstract: OBJECTIVE
  N-stearoyltyrosine (NsTyr) as an anandamide (AEA) analog has close relationships with AEA not only in structure but also in terms of biological actions of endocannabinoids. Since β-amyloid (Aβ)-induced primary neuronal injury involves the activation of the endocannabinoid systems (ECS), the protective effects of NsTyr against Aβ(1-40)-induced neuronal injury and the mechanism were studied systematically in this paper.
  
  
  METHODS
  Cortical neurons were incubated with Aβ(1-40) for 24 h. NsTyr was added to indicated concentrations 30 min prior to injury.
  
  
  RESULTS
  The best effects of NsTyr on Aβ(1-40)-induced primary neuronal injury occurred at 10 μM. The mechanism of NsTyr on neuroprotective effects against Aβ(1-40)-induced cellular death first involved anti-apoptosis resulting from the activation of cannabinoid receptors, then the pre-receptor regulation of AEA by the inhibition of endocannabinoid inactivation. These data demonstrated that the protective effects of NsTyr on Aβ(1-40)-induced primary neuronal injury resulted from the inhibition of fatty acid amide hydrolase (FAAH) (IC50=16.54 nM) and blocked AEA uptake mediated by anandamide membrane transporter (AMT) (IC50=11.74 nM).
  
  
  CONCLUSIONS
  The activation of ECS by inhibiting the degradation of AEA is an effective pharmacological approach to suppress Aβ-induced neuropathic injury. Our research could result in a more realistic alternative for AD treatment.
authors: Department of Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
authors: Hengjing
authors: H
authors: Cui
authors: Department of Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
authors: Rui
authors: R
authors: Yang
authors: Department of Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
authors: Sha
authors: S
authors: Liu
authors: Department of Pathology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
authors: Guohui
authors: G
authors: Fu
authors: Department of Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China. Electronic address: luyangssmu@163.com.
authors: Yang
authors: Y
authors: Lu
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001095:Arachidonic Acids / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D026901:Membrane Transport Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D016229:Amyloid beta-Peptides; D001095:Arachidonic Acids; D063388:Endocannabinoids; D026901:Membrane Transport Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D014443:Tyrosine; D000099252:Fatty Acid Amide Hydrolases; C078592:amyloid beta-protein (1-40); C087584:N-stearoyltyrosine; C078814:anandamide
keywords: Anandamide (AEA); Anandamide membrane transporter (AMT); Fatty acid amide hydrolase (FAAH); N-stearoyltyrosine (NsTyr); β-amyloid (Aβ)