Amyloid precursor protein metabolism is regulated toward alpha-secretase pathway by Ginkgo biloba extracts

Francesca Colciaghi, Barbara Borroni, Martina Zimmermann, Camilla Bellone, Annalisa Longhi, Alessandro Padovani, Flaminio Cattabeni, Yves Christen, Monica Di Luca

Research output: Contribution to journalArticle

Abstract

Clinical trials report that Ginkgo biloba extracts (e.g., EGb761) reduce cognitive symptoms in age-associated memory impairment and dementia, including Alzheimer disease (AD). However, the mechanisms behind their neuroprotective ability remain to be fully established. In this study, the effect of EGb761 on the amyloid precursor protein (APP) metabolism has been investigated by both in vitro and in vivo models. To this aim, alpha-secretase, the enzyme regulating the non-amyloidogenic processing of APP and the release of alphaAPPs, the alpha-secretase metabolite, were studied in superfusates of hippocampal slices after EGb761 incubation, and in hippocampi and cortices of EGb761-treated rats. PKC translocation state was evaluated as well. EGb761 increases alphaAPPs release through a PKC-independent manner. This effect is not accompanied by a modification of either APP forms or alpha-secretase expression. Moreover, EGb761 influence on alphaAPPs release was strictly dependent on treatment dosage. Our findings suggest that the benefit of EGb761 reported by previous clinical studies is underscored by a specific biological mechanism of this compound on APP metabolism, directly affecting the release of the non-amyloidogenic metabolite. Additional research will be needed to clearly define the effective clinical relevance, thus considering EGb761 as a possible supplementary treatment in dementing diseases.

Original languageEnglish
Pages (from-to)454-460
Number of pages7
JournalNeurobiology of Disease
Volume16
Issue number2
DOIs
Publication statusPublished - Jul 2004

Keywords

  • Alpha-secretase activity
  • Alzheimer disease
  • Amyloid precursor protein
  • Ginkgo biloba
  • PKC

ASJC Scopus subject areas

  • Neurology

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    Colciaghi, F., Borroni, B., Zimmermann, M., Bellone, C., Longhi, A., Padovani, A., Cattabeni, F., Christen, Y., & Di Luca, M. (2004). Amyloid precursor protein metabolism is regulated toward alpha-secretase pathway by Ginkgo biloba extracts. Neurobiology of Disease, 16(2), 454-460. https://doi.org/10.1016/j.nbd.2004.03.011