title: Chronic exposure to U18666A is associated with oxidative stress in cultured murine cortical neurons.
abstract: 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.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore.
authors.forename: Chor Hui Vivien
authors.initials: CH
authors.lastname: Koh
authors.forename: Matthew
authors.initials: M
authors.lastname: Whiteman
authors.forename: Qiao-Xin
authors.initials: QX
authors.lastname: Li
authors.forename: Barry
authors.initials: B
authors.lastname: Halliwell
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Jenner
authors.forename: Boon Seng
authors.initials: BS
authors.lastname: Wong
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Laughton
authors.forename: Markus
authors.initials: M
authors.lastname: Wenk
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.forename: Philip M
authors.initials: PM
authors.lastname: Beart
authors.forename: Ora
authors.initials: O
authors.lastname: Bernard
authors.forename: Nam Sang
authors.initials: NS
authors.lastname: Cheung
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000502:physiology; D000736:Androstenes / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D019636:Neurodegenerative Diseases / Q000473:pathology; D009474:Neurons / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D046988:Proteasome Endopeptidase Complex; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D016229:Amyloid beta-Peptides; D000736:Androstenes; D013778:Tetrazolium Salts; D013844:Thiazoles; C006261:3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one; D000255:Adenosine Triphosphate; D002784:Cholesterol; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D046988:Proteasome Endopeptidase Complex; C022616:thiazolyl blue; D005978:Glutathione