N-Stearoyltyrosine protects primary cortical neurons against Aβ(1-40)-induced injury through inhibiting endocannabinoid degradation.

AIMS

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.

MAIN METHODS

Cortical neurons were incubated with Aβ(1-40) for 24 h. NsTyr was added to indicated concentrations 30 min prior to injury.

KEY FINDINGS

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).

SIGNIFICANCE

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.