Anandamide and noladin ether prevent neurotoxicity of the human amyloid-beta peptide

Cannabinoid receptor agonists including anandamide and noladin either have recently been suggested to exhibit neuroprotective properties. The amyloid-beta (Abeta) peptide is thought to be responsible for the neurodegenerative changes associated with Alzheimer's disease pathology. This study characterizes the effects of anandamide and noladin ether on the neurotoxicity of Abeta in differentiated human teratocarcinoma cell line, Ntera 2/cl-D1 neurons. Anandamide and noladin ether, at nanomolar concentrations, showed concentration dependent inhibition of Abeta toxicity. A CB(1) cannabinoid receptor antagonist, AM251, prevented the protective effects of anandamide and noladin ether. The mitogen activated protein kinase (MAPK) pathway inhibitor PD98059 also prevented the protective effects of cannabinoids and corticotrophin-releasing hormone. These results suggest that activation of the MAPK pathway by either cannabinoids or corticotrophin-releasing hormone could be used to prevent Abeta peptide induced neurodegeneration.