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P4–301: Nicotinic component of galantamine in the regulation of amyloid precursor protein processing
Author(s) -
Govoni Stefano M.,
Lenzken Silvia Carolina,
Lanni Cristina,
Mazzucchelli Michela,
Porrello Emanuela,
Racchi Marco
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.2042
Subject(s) - cholinergic , muscarinic acetylcholine receptor , nicotinic agonist , acetylcholinesterase , amyloid precursor protein , galantamine , western blot , acetylcholine , chemistry , receptor , protein kinase c , endocrinology , medicine , biology , signal transduction , microbiology and biotechnology , biochemistry , donepezil , alzheimer's disease , enzyme , dementia , disease , gene
Current therapies for Alzheimer's disease treatment rely mainly on acetylcholinesterase inhibitors, improving central cholinergic neurotransmission. Among these molecules, galantamine (GAL) has an interesting pharmacological profile as it is both a reversible acetylcholinesterase inhibitor and an allosteric potentiator of nicotinic cholinergic receptors. We investigated the effect of GAL on the metabolism of the amyloid precursor protein (APP) in differentiated SH-SY5Y neuroblastoma cells. The rationale was based on the suggestion that cholinergic activity may also be involved in the regulation of APP metabolism. We studied the acute effect on APP metabolism measuring the secretion of sAPPalpha in the conditioned medium of cells. Following 2h treatment, GAL 10microM promoted a strong increase in the release of sAPPalpha, the maximal effect approaching on average three-fold baseline value. The compound appeared to increase the release of sAPPalpha, with a mechanism dependent upon an indirect cholinergic stimulation. The effect of GAL was prevented by pre-treatment with alpha-bungarotoxin (40nM) but not low (nanomolar) atropine concentrations, suggesting the specific involvement of nicotinic cholinergic receptors.