N-Acetyl-L-Cystein downregulates beta-amyloid precursor protein gene transcription in human neuroblastoma cells.
The causes for the sporadic form of Alzheimer's disease (AD) are still poorly understood, except from the fact that age is an important risk factor. The main component of the characteristic amyloid plaques in brains of AD patients are Abeta peptides, derivatives of the amyloid precursor protein APP. Oxidative stress may contribute to the aetiology of AD by dysregulation of APP metabolism. Overexpression of the APP gene could result in an increased secretion of neurotoxic Abeta peptides, while preventing the overexpression might be protective. We here report that the antioxidant N-Acetyl-L-Cystein (NAC) downregulates APP gene transcription in human neuroblastoma cells. The effect is reversible when cells are returned to NAC free medium. These results open up new possibilities for the development of therapeutic agents that intervene at the transcriptional level.
Studer
R
R
Laboratory of Molecular Gerontology, Basel University, Psychiatric University Clinic, Switzerland. Rolf.Studer@Actelion.Com
Baysang
G
G
Brack
C
C
D000111:Acetylcysteine / Q000494:pharmacology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000975:Antioxidants / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D009447:Neuroblastoma; D018384:Oxidative Stress; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D016564:Amyloid beta-Protein Precursor; D000975:Antioxidants; D000111:Acetylcysteine