Chronic exposure to U18666A is associated with oxidative stress in cultured murine cortical neurons

J Neurochem. 2006 Aug;98(4):1278-89. doi: 10.1111/j.1471-4159.2006.03958.x. Epub 2006 Jun 12.


Findings that antioxidant treatment may be beneficial in Alzheimer's disease indicate that oxidative stress is an important factor in its pathogenesis. Studies have also suggested that cholesterol imbalance in the brain might be related to the development of neurological disorders. Previously, we have reported that U18666A, a cholesterol transport-inhibiting agent, leads to apoptosis and intracellular cholesterol accumulation in primary cortical neurons. In this study, we found that neuronal apoptosis mediated by U18666A is associated with oxidative stress in the treated cortical neurons. Cortical neurons treated with U18666A also showed decreased secretion and increased intraneuronal accumulation of beta-amyloid. The association of neuronal apoptosis with oxidative stress and Abeta accumulation may provide clues to the pathogenesis of Alzheimer's disease, as well as the role oxidative stress plays in other neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amyloid beta-Peptides / physiology
  • Androstenes / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Blotting, Western
  • Caspase 3
  • Caspases / metabolism
  • Cells, Cultured
  • Cerebral Cortex / cytology*
  • Cerebral Cortex / drug effects
  • Cholesterol / metabolism
  • Gas Chromatography-Mass Spectrometry
  • Glutathione / metabolism
  • Lipid Peroxidation / drug effects
  • Membrane Potentials / drug effects
  • Mice
  • Neurodegenerative Diseases / pathology
  • Neurons / drug effects*
  • Oxidative Stress / drug effects*
  • Proteasome Endopeptidase Complex
  • Tetrazolium Salts
  • Thiazoles


  • Amyloid beta-Peptides
  • Androstenes
  • Tetrazolium Salts
  • Thiazoles
  • 3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one
  • Adenosine Triphosphate
  • Cholesterol
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases
  • Proteasome Endopeptidase Complex
  • thiazolyl blue
  • Glutathione