Prolyl Oligopeptidase, Inositol Phosphate Signalling and Lithium Sensitivity

Abstract

An intriguing aspect of prolyl oligopeptidase (PO) biology is its relationship with bipolar mood disorder and lithium (Li+) sensitivity. Bipolar mood disorder, also know as manic-depression, is a prevalent mental illness with a significant socio-economic impact. The biological causes of this major mental disorder remain unknown and, despite a strong genetic evidence for predisposition, there are currently no universally agreed consensus candidate genes that confer risk. Li+ is the most commonly used mood stabilizer used in the treatment of bipolar mood disorder and is particularly useful as a prophylactic, suppressing the re-occurrence of the illness. However, Li+ is taken in high doses, has side-effects and is not effective in all cases. Although a number of enzyme targets have been well characterised, how Li+ treatment mediates its action also remains unknown. This review describes recent results investigating how PO modulates cell sensitivity to Li+, and how this may relate to the treatment and molecular origins of bipolar mood disorder.