4.4 Article

Validating GSK3 as an in vivo target of lithium action

Journal

BIOCHEMICAL SOCIETY TRANSACTIONS
Volume 37, Issue -, Pages 1133-1138

Publisher

PORTLAND PRESS LTD
DOI: 10.1042/BST0371133

Keywords

behaviour; bipolar disorder; glycogen synthase kinase 3 (GSK3); inositol; lithium; Wnt

Funding

  1. National Institutes of Health/National Institute of Mental Health [R01MH058324]
  2. American Federation for Aging Research

Ask authors/readers for more resources

Lithium is widely used to treat bipolar disorder, but its mechanism of action in this disorder is unknown. Lithium directly inhibits GSK3 (glycogen synthase kinase 3), a critical regulator of multiple signal transduction pathways. inhibition of GSK3 provides a compelling explanation for many of the known effects of lithium, including effects on early development and insulin signalling/glycogen synthesis. However, lithium also inhibits inositol monophosphatase, several structurally related phosphomonoesterases, phosphoglucomutase and the scaffolding function of beta-arrestin-2. It is not known which of these targets is responsible for the behavioural or therapeutic effects of lithium in vivo. The present review discusses basic criteria that can be applied to model systems to validate a proposed direct target of lithium. in this context, we describe a set of simple behaviours in mice that are robustly affected by chronic lithium treatment and are similarly affected by structurally diverse GSK3 inhibitors and by removing one copy of the Gsk3b gene. These observations, from several independent laboratories, support a central role for GSK3 in mediating behavioural responses to lithium.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.4
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available