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Prolyl Oligopeptidase, Inositol Phosphate Signalling and Lithium Sensitivity

[ Vol. 10 , Issue. 3 ]

Author(s):

Adrian J. Harwood   Pages 333 - 339 ( 7 )

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)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

Affiliation:

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



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