Galantamine inhibits beta-amyloid aggregation and cytotoxicity.
The ability of galantamine (Reminyl) to inhibit the aggregation and toxicity of the beta-amyloid peptide (Abeta) was investigated. Galantamine showed concentration-dependent inhibition of aggregation of both Abeta 1-40 and Abeta 1-42, as determined by an ELISA method. Electron microscope studies of Abeta 1-40 incubated in the presence of galantamine revealed fibrils that were disordered and clumped in appearance. MTT and lactate dehydrogenase assays, employing SH-SY5Y human neuroblastoma cells, showed that galantamine reduced the cytotoxicity induced by Abeta 1-40. Galantamine also dramatically reduced Abeta 1-40-induced cellular apoptosis in these cells. There is some evidence that galantamine may not be acting purely as a symptomatic treatment. Disease-modifying effects of the drug could be due to an additional effect on Abeta aggregation and/or toxicity.
Matharu
Balpreet
B
Neurodegeneration Unit, Basic Medical Sciences, St. George's University of London, Cranmer Terrace, Tooting, London SW17 0RE, UK.
Gibson
Gillian
G
Parsons
Richard
R
Huckerby
Thomas N
TN
Moore
Susan A
SA
Cooper
Leanne J
LJ
Millichamp
Robert
R
Allsop
David
D
Austen
Brian
B
D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000378:metabolism / Q000633:toxicity; D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005702:Galantamine / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008854:Microscopy, Electron; D008958:Models, Molecular; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000187:drug effects* / Q000378:metabolism / Q000633:toxicity
D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D005702:Galantamine; D007770:L-Lactate Dehydrogenase