NGF promotes amyloid precursor protein secretion via muscarinic receptor activation.
Processing of beta-amyloid precursor protein (APP) is coupled to several neurotransmitter receptors, including m1 muscarinic (m1AChR), and is associated with decreased amyloid deposition. Muscarinic agonist-stimulated APP secretion and membrane APP were measured in control and in NGF-differentiated PC12 cells stably transfected with m1AChR. This secretion was markedly enhanced following treatment with 50 ng/ml NGF for 3 days, and was observed using either carbachol or the M1-selective agonist AF102B. The effects of NGF were reflected by larger reductions in membrane-associated APP levels following muscarinic stimulation. These observations imply that M1 muscarinic receptors may act in concert with NGF to boost APP processing, and M1-selective agonists may thus be beneficial for reducing amyloid deposition by NGF-responsive neurons.
Haring
R
R
Israel Institute for Biological Research, Ness-Ziona.
Gurwitz
D
D
Barg
J
J
Pinkas-Kramarski
R
R
Heldman
E
E
Pittel
Z
Z
Danenberg
H D
HD
Wengier
A
A
Meshulam
H
H
Marciano
D
D
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells; D010277:Parasympathomimetics / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013876:Thiophenes; D013997:Time Factors; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D009414:Nerve Growth Factors; D010277:Parasympathomimetics; D011812:Quinuclidines; D011976:Receptors, Muscarinic; D011994:Recombinant Proteins; D013876:Thiophenes; D002217:Carbachol; C059240:cevimeline; D013755:Tetradecanoylphorbol Acetate