Pathological Defects in a Drosophila Model of Alzheimer's Disease and Beneficial Effects of the Natural Product Lisosan G

果蝇阿尔茨海默病模型中的病理缺陷和天然产物 Lisosan G 的有益作用

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作者:Silvia Bongiorni, Elisabetta Catalani, Ivan Arisi, Francesca Lazzarini, Simona Del Quondam, Kashi Brunetti, Davide Cervia, Giorgio Prantera

Abstract

Alzheimer's disease (AD) brains are histologically marked by the presence of intracellular and extracellular amyloid deposits, which characterize the onset of the disease pathogenesis. Increasing evidence suggests that certain nutrients exert a direct or indirect effect on amyloid β (Aβ)-peptide production and accumulation and, consequently, on AD pathogenesis. We exploited the fruit fly Drosophila melanogaster model of AD to evaluate in vivo the beneficial properties of Lisosan G, a fermented powder obtained from organic whole grains, on the intracellular Aβ-42 peptide accumulation and related pathological phenotypes of AD. Our data showed that the Lisosan G-enriched diet attenuates the production of neurotoxic Aβ peptides in fly brains and reduces neuronal apoptosis. Notably, Lisosan G exerted anti-oxidant effects, lowering brain levels of reactive oxygen species and enhancing mitochondrial activity. These aspects paralleled the increase in autophagy turnover and the inhibition of nucleolar stress. Our results give support to the use of the Drosophila model not only to investigate the molecular genetic bases of neurodegenerative disease but also to rapidly and reliably test the efficiency of potential therapeutic agents and diet regimens.

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