title: Prolyl oligopeptidase, inositol phosphate signalling and lithium sensitivity.
abstract: Inhibition of prolyl oligopeptidase (PO) elevates inositol phosphate (IP) signalling and reduces cell sensitivity to lithium (Li+). This review discusses recent evidence that shows PO acts via the multiple inositol polyphosphate phosphatase (MIPP) to regulate gene expression. As a consequence, PO inhibition causes both a transient, rapid increase in I(1,4,5)P(3) and a long-term elevation of IP signalling. This pathway is evolutionary conserved, being present in both the social amoeba Dictyostelium and human cell systems, and has potential implications for mental health.
authors.affiliation: School of Biosciences, Cardiff University, UK. harwoodaj@cardiff.ac.uk
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Harwood
mesh_terms: D004023:Dictyostelium / Q000187:drug effects / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007295:Inositol Phosphates / Q000235:genetics / Q000502:physiology*; D016651:Lithium Carbonate / Q000494:pharmacology*; D058990:Molecular Targeted Therapy; D000085822:Prolyl Oligopeptidases; D011528:Protozoan Infections / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D007295:Inositol Phosphates; D016651:Lithium Carbonate; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases