Obestatin promotes proliferation and survival of adult hippocampal progenitors and reduces amyloid-β-induced toxicity

The ghrelin gene-derived peptide obestatin promotes survival in different cell types through a Stet 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 G alpha s/AMP/PKA/CREB signaling, phosphorylation of ERK1/2 and PI3K/Alct, and the PI3K targets GSK-3 beta/beta-catenin and mTOR. Obestatin also counteracted A beta(1-42)-induced detrimental effects through inhibition of GSK-3 beta 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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.