title: Obestatin promotes proliferation and survival of adult hippocampal progenitors and reduces amyloid-β-induced toxicity.
abstract: The ghrelin gene-derived peptide obestatin promotes survival in different cell types through a yet undefined receptor; however, its potential neuroprotective activities are still unknown. Here, obestatin effects were investigated on proliferation and survival of adult rat hippocampal progenitor cells (AHPs). Obestatin immunoreactivity was found in AHPs; moreover, obestatin binding to AHPs was displaced by the GLP-1R agonist Ex-4 and antagonist Ex-9. Furthermore, obestatin increased cell proliferation and survival in growth factor deprived medium and inhibited apoptosis; these effects were blocked by Ex-9. The underlying mechanisms involved Gαs/cAMP/PKA/CREB signaling, phosphorylation of ERK1/2 and PI3K/Akt, and the PI3K targets GSK-3β/β-catenin and mTOR. Obestatin also counteracted Aβ1-42-induced detrimental effects through inhibition of GSK-3β activity and Tau hyperphosphorylation, main hallmarks of neuronal death in Alzheimer's disease. These findings indicate a novel protective role for obestatin in AHPs and candidate this peptide as potential therapeutic target for increasing neurogenesis and for approaching neurodegenerative disorders.
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, University of Torino, 10126 Torino, Italy; Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Gargantini
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, University of Torino, 10126 Torino, Italy; Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Lazzari
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, University of Torino, 10126 Torino, Italy; Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Settanni
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, University of Torino, 10126 Torino, Italy; Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Taliano
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, University of Torino, 10126 Torino, Italy; Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Trovato
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, University of Torino, 10126 Torino, Italy; Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Iacopo
authors.initials: I
authors.lastname: Gesmundo
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Ezio
authors.initials: E
authors.lastname: Ghigo
authors.affiliation: Laboratory of Molecular and Cellular Endocrinology, University of Torino, 10126 Torino, Italy; Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Torino, 10126 Torino, Italy. Electronic address: riccarda.granata@unito.it.
authors.forename: Riccarda
authors.initials: R
authors.lastname: Granata
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000077270:Exenatide; D006624:Hippocampus / Q000166:cytology*; D036361:Peptide Hormones / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014688:Venoms / Q000494:pharmacology; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C489131:Mapt protein, rat; D036361:Peptide Hormones; D010455:Peptides; D014688:Venoms; C505798:obestatin, rat; D016875:tau Proteins; D000077270:Exenatide
keywords: Amyloid beta peptide; Cell survival; GSK-3β/β-catenin; Hippocampal progenitors; Obestatin; PI3K/Akt