Nerve growth factor modulates the expression and secretion of beta-amyloidprecursor protein through different mechanisms in PC12 cells

Citation
A. Villa et al., Nerve growth factor modulates the expression and secretion of beta-amyloidprecursor protein through different mechanisms in PC12 cells, J NEUROCHEM, 77(4), 2001, pp. 1077-1084
Citations number
52
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROCHEMISTRY
ISSN journal
0022-3042 → ACNP
Volume
77
Issue
4
Year of publication
2001
Pages
1077 - 1084
Database
ISI
SICI code
0022-3042(200105)77:4<1077:NGFMTE>2.0.ZU;2-W
Abstract
The beta -amyloid protein, component of the senile plaques found in Alzheim er brains is proteolytically derived from the beta -amyloid precursor prote in (APP), a larger membrane-associated protein that is expressed in both ne ural and nonneural cells. Overexpression of APP might be one of the mechani sms that more directly contributes to the development of Alzheimer's diseas e. The APP gene expression is regulated by a number of cellular mediators i ncluding nerve growth factor (NGF) and other ligands of tyrosine kinase rec eptors. We have previously described that NGF increases APP mRNA levels in PC12 cells. However, the molecular mechanisms and the precise signalling pa thways that mediate its regulation are not yet well understood. In the pres ent study we present evidence that NGF, and to a lesser extent fibroblast g rowth factor and epidermal growth factor, stimulate APP promoter activity i n PC12 cells. This induction is mediated by DNA sequences located between t he nucleotides - 307 and - 15, and involves activation of the Has-MAP kinas e signalling pathway. In contrast, we have also found that NGF-induced secr etion of soluble fragments of APP into the culture medium is mediated by a Ras independent mechanism.