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CNS & Neurological Disorders - Drug Targets


ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Prolyl Oligopeptidase, Inositol Phosphate Signalling and Lithium Sensitivity

Author(s): Adrian J. Harwood

Volume 10 , Issue 3 , 2011

Page: [333 - 339] Pages: 7

DOI: 10.2174/187152711794653779


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)P3 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.

Keywords: Bipolar mood disorder, Dictyostelium, inositol phosphate signalling, lithium, multiple inositol polyphosphate phosphatase, prolyl oligopeptidase, IMPase, LY294002, GSK-3, MIPP, ISYNA1

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