title: Effects of Ghrelin on the Proteolytic Pathways of Alzheimer's Disease Neuronal Cells.
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.
authors.affiliation: School of Biosciences and Veterinary Medicine, University of Camerino, 62032, Camerino, Italy. valentina.cecarini@unicam.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cecarini
authors.affiliation: School of Biosciences and Veterinary Medicine, University of Camerino, 62032, Camerino, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bonfili
authors.affiliation: School of Biosciences and Veterinary Medicine, University of Camerino, 62032, Camerino, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cuccioloni
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Keller
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
authors.forename: Annadora J
authors.initials: AJ
authors.lastname: Bruce-Keller
authors.affiliation: School of Biosciences and Veterinary Medicine, University of Camerino, 62032, Camerino, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Eleuteri
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1 / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D054439:Ghrelin / Q000494:pharmacology*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects*; D054440:Receptors, Ghrelin / Q000378:metabolism; D000071456:Sequestosome-1 Protein / Q000378:metabolism; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D000071186:Beclin-1; D054439:Ghrelin; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D054440:Receptors, Ghrelin; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D025801:Ubiquitin; D050760:Cyclin-Dependent Kinase Inhibitor p27; D002401:Cathepsin B; D046988:Proteasome Endopeptidase Complex
keywords: Alzheimer’s disease; Autophagy; Ghrelin; Proteasome