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Effects of Ghrelin on the Proteolytic Pathways of Alzheimer’s Disease Neuronal Cells

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Abstract

Ghrelin is an orexigenic hormone with a role in the onset and progression of neurodegenerative disorders. It has been recently associated to Alzheimer’s disease (AD) for its neuroprotective and anti-apoptotic activity. In the present study, we dissected the effect of ghrelin treatment on the two major intracellular proteolytic pathways, the ubiquitin-proteasome system (UPS) and autophagy, in cellular models of AD (namely SH-SY5Y neuroblastoma cells stably transfected with either the wild-type AβPP gene or the 717 valine-to-glycine AβPP-mutated gene). Ghrelin showed a growth-promoting effect on neuronal cells inducing also time-dependent modifications of the growth hormone secretagogue receptor type 1 (GHS-R1) expression. Interestingly, we demonstrated for the first time that ghrelin was able to activate the proteasome in neural cells playing also a role in the interplay between the UPS and autophagy. Our data provide a novel mechanism by which circulating hormones control neural homeostasis through the regulation of proteolytic pathways implicated in AD.

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Abbreviations

UPS:

Ubiquitin-proteasome system

GHS-R1:

Growth hormone secretagogue receptor type 1

GOAT:

Ghrelin O-acyltransferase

Aβ:

Amyloid-β

AβPP:

Amyloid-β precursor protein

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The authors declare that they have no competing interests.

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Authors and Affiliations

  1. School of Biosciences and Veterinary Medicine, University of Camerino, 62032, Camerino, Italy

    Valentina Cecarini, Laura Bonfili, Massimiliano Cuccioloni & Anna Maria Eleuteri

  2. Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA

    Jeffrey N. Keller & Annadora J. Bruce-Keller

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  1. Valentina Cecarini
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  2. Laura Bonfili
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  3. Massimiliano Cuccioloni
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  4. Jeffrey N. Keller
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  6. Anna Maria Eleuteri
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Correspondence to Valentina Cecarini.

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Cecarini, V., Bonfili, L., Cuccioloni, M. et al. Effects of Ghrelin on the Proteolytic Pathways of Alzheimer’s Disease Neuronal Cells. Mol Neurobiol 53, 3168–3178 (2016). https://doi.org/10.1007/s12035-015-9227-x

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