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

Authors

Chor Koh, National University of Singapore
Matthew Whiteman, National University of Singapore
Qiao-Xin Li, University of Melbourne
Barry Halliwell, National University of SingaporeFollow
Andrew Jenner, University of WollongongFollow
Boon Wong, National University of Singapore
Katrina Laughton, University of Melbourne
Markus Wenk, Dept of Biochemistry, National Uni of Singapore
Colin Masters, University of Melbourne
Philip Beart, Howard Florey Institute, Uni of Melbourne
Ora Bernard, Royal Melbourne Hospital
Nam Cheung, National University of Singapore

RIS ID

39092

Publication Details

Koh, C., Whiteman, M., Li, Q., Halliwell, B., Jenner, A., Wong, B., Laughton, K., Wenk, M., Masters, C., Beart, P., Bernard, O. & Cheung, N. (2006). Chronic exposure to U18666A is associated with oxidative stress in cultured murine cortical neurons. Journal of Neurochemistry, 98 (4), 1278-1289.

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 β-amyloid. The association of neuronal apoptosis with oxidative stress and Aβ accumulation may provide clues to the pathogenesis of Alzheimer's disease, as well as the role oxidative stress plays in other neurodegenerative diseases.