Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Galantamine inhibits β-amyloid aggregation and cytotoxicity
AU - Matharu, Balpreet
AU - Gibson, Gillian
AU - Parsons, Richard
AU - Huckerby, Thomas N
AU - Moore, Susan A
AU - Cooper, Leanne J
AU - Millichamp, Robert
AU - Allsop, David
AU - Austen, Brian
PY - 2009/5/15
Y1 - 2009/5/15
N2 - 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.
AB - 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.
KW - Amyloid beta-Peptides
KW - Analysis of Variance
KW - Apoptosis
KW - Cell Line, Tumor
KW - Cholinesterase Inhibitors
KW - Dose-Response Relationship, Drug
KW - Enzyme-Linked Immunosorbent Assay
KW - Galantamine
KW - Humans
KW - L-Lactate Dehydrogenase
KW - Microscopy, Electron
KW - Models, Molecular
KW - Neuroprotective Agents
KW - Nuclear Magnetic Resonance, Biomolecular
KW - Peptide Fragments
U2 - 10.1016/j.jns.2009.01.024
DO - 10.1016/j.jns.2009.01.024
M3 - Journal article
C2 - 19249060
VL - 280
SP - 49
EP - 58
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
IS - 1-2
ER -