Ginkgolide B inhibits the neurotoxicity of prions or amyloid-β_1-42

• Main Authors: Williams Alun, Salmona Mario, Bate Clive
• Format: Article
• Language: English
• Published: BMC 2004-05-01
• Series: Journal of Neuroinflammation
• Online Access: http://www.jneuroinflammation.com/content/1/1/4

<p>Abstract</p> <p>Background</p> <p>Neuronal loss in Alzheimer's or prion diseases is preceded by the accumulation of fibrillar aggregates of toxic proteins (amyloid-β_1-42or the prion protein). Since some epidemiological studies have demonstrated that the EGb 761 extract, from the leaves of the <it>Ginkgo biloba </it>tree, has a beneficial effect on Alzheimer's disease, the effect of some of the major components of the EGb 761 extract on neuronal responses to amyloid-β_1-42, or to a synthetic miniprion (sPrP106), were investigated.</p> <p>Methods</p> <p>Components of the EGb 761 extract were tested in 2 models of neurodegeneration. SH-SY5Y neuroblastoma cells were pre-treated with ginkgolides A or B, quercetin or myricetin, and incubated with amyloid-β_1-42, sPrP106, or other neurotoxins. After 24 hours neuronal survival and the production of prostaglandin E₂that is closely associated with neuronal death was measured. In primary cortical neurons apoptosis (caspase-3) in response to amyloid-β_1-42or sPrP106 was measured, and in co-cultures the effects of the ginkgolides on the killing of amyloid-β_1-42or sPrP106 damaged neurons by microglia was tested.</p> <p>Results</p> <p>Neurons treated with ginkgolides A or B were resistant to amyloid-β_1-42or sPrP106. Ginkgolide-treated cells were also resistant to platelet activating factor or arachidonic acid, but remained susceptible to hydrogen peroxide or staurosporine. The ginkgolides reduced the production of prostaglandin E₂in response to amyloid-β_1-42or sPrP106. In primary cortical neurons, the ginkgolides reduced caspase-3 responses to amyloid-β_1-42or sPrP106, and in co-culture studies the ginkgolides reduced the killing of amyloid-β_1-42or sPrP106 damaged neurons by microglia.</p> <p>Conclusion</p> <p>Nanomolar concentrations of the ginkgolides protect neurons against the otherwise toxic effects of amyloid-β_1-42or sPrP106. The ginkgolides also prevented the neurotoxicity of platelet activating factor and reduced the production of prostaglandin E₂in response to platelet activating factor, amyloid-β_1-42or sPrP106. These results are compatible with prior reports that ginkgolides inhibit platelet-activating factor, and that platelet-activating factor antagonists block the toxicity of amyloid-β_1-42or sPrP106. The results presented here suggest that platelet-activating factor antagonists such as the ginkgolides may be relevant treatments for prion or Alzheimer's diseases.</p>