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Nerve growth factor and ras regulate beta-amyloid precursor protein gene expression in PC12 cells
J M Cosgaya1, M J Latasa, A Pascual
1Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Journal of Neurochemistry
|July 1, 1996
Summary
Nerve growth factor (NGF) and other growth factors increase beta-amyloid precursor protein (APP) gene expression in PC12 cells. The ras signaling pathway mediates this induction, suggesting a role in Alzheimer's disease pathology.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Alzheimer's disease is characterized by beta-amyloid deposits.
- Beta-amyloid precursor protein (APP) expression is linked to Alzheimer's pathology.
- Mechanisms regulating APP gene expression are not fully understood.
Purpose of the Study:
- To investigate the regulation of APP gene expression.
- To determine the role of nerve growth factor (NGF) in APP expression.
- To elucidate the involvement of the ras signaling pathway in APP gene regulation.
Main Methods:
- Utilized PC12 cells and a UR61 subline.
- Administered NGF, fibroblast growth factor, and epidermal growth factor.
- Assessed APP mRNA levels and the effect of ras mutants.
Main Results:
- NGF significantly increased APP gene expression and mRNA levels in PC12 cells.
- Activated ras expression also increased APP transcripts.
- A dominant negative ras mutant inhibited NGF-induced APP expression.
Conclusions:
- The ras signaling pathway mediates NGF-induced APP gene expression.
- Other tyrosine kinase receptor ligands also increase APP mRNA levels via ras.
- These findings suggest a mechanism for APP regulation relevant to Alzheimer's disease.