title: Amyloid precursor protein metabolism is regulated toward alpha-secretase pathway by Ginkgo biloba extracts.
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.
authors.affiliation: Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological Sciences, University of Milan, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Colciaghi
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
authors.forename: Martina
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Camilla
authors.initials: C
authors.lastname: Bellone
authors.forename: Annalisa
authors.initials: A
authors.lastname: Longhi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.forename: Flaminio
authors.initials: F
authors.lastname: Cattabeni
authors.forename: Yves
authors.initials: Y
authors.lastname: Christen
authors.forename: Monica
authors.initials: M
authors.lastname: Di Luca
mesh_terms: D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D010450:Endopeptidases / Q000378:metabolism*; D020441:Ginkgo biloba; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D009924:Organ Culture Techniques; D010936:Plant Extracts / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000096983:Ginkgo Extract
chemical_list: D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor; D010450:Endopeptidases; D010936:Plant Extracts; D011493:Protein Kinase C; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract