alpha 7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block a beta-amyloid-induced neurotoxicity

Citation
T. Kihara et al., alpha 7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block a beta-amyloid-induced neurotoxicity, J BIOL CHEM, 276(17), 2001, pp. 13541-13546
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
276
Issue
17
Year of publication
2001
Pages
13541 - 13546
Database
ISI
SICI code
0021-9258(20010427)276:17<13541:A7NRTS>2.0.ZU;2-J
Abstract
Multiple lines of evidence, from molecular and cellular to epidemiological, have implicated nicotinic transmission in the pathogenesis of Alzheimer's disease (AD). Here we show the signal transduction mechanism involved in ni cotinic receptor-mediated protection against beta -amyloid-enhanced glutama te neurotoxicity. Nicotine-induced protection was suppressed by an alpha7 n icotinic receptor antagonist (alpha -bungarotoxin), a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002 and wortmannin), and a Src inhibitor (P P2). Levels of phosphorylated Akt, an effector of PI3K, and Bcl-2 were incr eased by nicotine. The alpha7 nicotinic receptor was physically associated with the PI3K p85 subunit and Fyn. These findings indicate that the alpha7 nicotinic receptor trans duces signals to PI3K in a cascade, which ultimate ly contributes to a neuroprotective effect. This might form the basis of a new treatment for AD.