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

Neurosci Lett. 2002 Oct 31;332(2):127-30. doi: 10.1016/s0304-3940(02)00936-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / toxicity*
  • Arachidonic Acids / pharmacology*
  • Cannabinoids / pharmacology*
  • Corticotropin-Releasing Hormone / pharmacology
  • Endocannabinoids
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Glycerides / pharmacology*
  • Humans
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Nervous System Diseases / chemically induced*
  • Nervous System Diseases / prevention & control*
  • Neurons / drug effects
  • Neurons / pathology
  • Neuroprotective Agents*
  • Neurotoxins / antagonists & inhibitors*
  • Neurotoxins / toxicity*
  • Oxidation-Reduction
  • Peptide Fragments / antagonists & inhibitors*
  • Peptide Fragments / pharmacology
  • Peptide Fragments / toxicity*
  • Polyunsaturated Alkamides
  • Receptors, Cannabinoid
  • Receptors, Drug / antagonists & inhibitors

Substances

  • Amyloid beta-Peptides
  • Arachidonic Acids
  • Cannabinoids
  • Endocannabinoids
  • Enzyme Inhibitors
  • Flavonoids
  • Glycerides
  • Neuroprotective Agents
  • Neurotoxins
  • Peptide Fragments
  • Polyunsaturated Alkamides
  • Receptors, Cannabinoid
  • Receptors, Drug
  • amyloid beta-protein (1-40)
  • noladin ether
  • Corticotropin-Releasing Hormone
  • corticotropin releasing hormone (9-41)
  • Mitogen-Activated Protein Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • anandamide