4.5 Article

Galantamine inhibits β-amyloid aggregation and cytotoxicity

Journal

JOURNAL OF THE NEUROLOGICAL SCIENCES
Volume 280, Issue 1-2, Pages 49-58

Publisher

ELSEVIER
DOI: 10.1016/j.jns.2009.01.024

Keywords

Amyloid oligomers; Galantamine, Neurotoxicity; Alzheimer's; Acetylcholinesterase

Funding

  1. The Alzheimer's Society
  2. The Wellcome Trust [066268/Z/01/Z]
  3. Friends of Lytham Hospital and The Healthcare Foundation

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The ability of galantamine (Reminyl (R)) to inhibit the aggregation and toxicity of the beta-amyloid peptide (A beta) was investigated. Galantamine showed concentration-dependent inhibition of aggregation of both A beta 1-40 and A beta 1-42, as determined by an ELISA method. Electron microscope studies of A beta 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 A beta 1-40. Galantamine also dramatically reduced A beta 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 A beta aggregation and/or toxicity. (C) 2009 Elsevier B.V. All rights reserved.

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