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Plant sphingolipids promote extracellular vesicle release and alleviate amyloid-? pathologies in a mouse model of Alzheimer's disease.


ABSTRACT: The accumulation of amyloid-? protein (A?) in brain is linked to the early pathogenesis of Alzheimer's disease (AD). We previously reported that neuron-derived exosomes promote A? clearance in the brains of amyloid precursor protein transgenic mice and that exosome production is modulated by ceramide metabolism. Here, we demonstrate that plant ceramides derived from Amorphophallus konjac, as well as animal-derived ceramides, enhanced production of extracellular vesicles (EVs) in neuronal cultures. Oral administration of plant glucosylceramide (GlcCer) to APP overexpressing mice markedly reduced A? levels and plaque burdens and improved cognition in a Y-maze learning task. Moreover, there were substantial increases in the neuronal marker NCAM-1, L1CAM, and A? in EVs isolated from serum and brain tissues of the GlcCer-treated AD model mice. Our data showing that plant ceramides prevent A? accumulation by promoting EVs-dependent A? clearance in vitro and in vivo provide evidence for a protective role of plant ceramides in AD. Plant ceramides might thus be used as functional food materials to ameliorate AD pathology.

SUBMITTER: Yuyama K 

PROVIDER: S-EPMC6856149 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Plant sphingolipids promote extracellular vesicle release and alleviate amyloid-β pathologies in a mouse model of Alzheimer's disease.

Yuyama Kohei K   Takahashi Kaori K   Usuki Seigo S   Mikami Daisuke D   Sun Hui H   Hanamatsu Hisatoshi H   Furukawa Junichi J   Mukai Katsuyuki K   Igarashi Yasuyuki Y  

Scientific reports 20191114 1


The accumulation of amyloid-β protein (Aβ) in brain is linked to the early pathogenesis of Alzheimer's disease (AD). We previously reported that neuron-derived exosomes promote Aβ clearance in the brains of amyloid precursor protein transgenic mice and that exosome production is modulated by ceramide metabolism. Here, we demonstrate that plant ceramides derived from Amorphophallus konjac, as well as animal-derived ceramides, enhanced production of extracellular vesicles (EVs) in neuronal culture  ...[more]

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