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Prolyl Oligopeptidase, Inositol Phosphate Signalling and Lithium Sensitivity

[ Vol. 10 , Issue. 3 ]


Adrian J. Harwood   Pages 333 - 339 ( 7 )


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.


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


School of Biosciences, Cardiff University, Museum Ave, Cardiff, CF10 3AX, UK.

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