Lithium therapy and signal transduction.
Lithium is the simplest therapeutic agent available for the treatment of depression and has been used for over 100 years, yet no definitive mechanism for its effect has been established. Among the proposed mechanisms, two lithium-sensitive signal transduction pathways are active in the brain; these are mediated by glycogen synthase kinase 3beta (GSK-3beta) and inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3] signalling. This article describes recent experiments in cell and developmental biology that advance our understanding of how lithium works and it presents new directions for the study of both depression and Alzheimer's disease (AD).
Williams
R S
RS
MRC Laboratory for Molecular Cell Biology and Department of Biology, University College London, Gower St, London, UK WC1E 6BT. robin.williams@ucl.ac.uk
Harwood
A J
AJ
D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D003863:Depression / Q000188:drug therapy; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008094:Lithium / Q000627:therapeutic use*; D019964:Mood Disorders / Q000201:enzymology / Q000378:metabolism; D009434:Neural Pathways / Q000187:drug effects; D000085822:Prolyl Oligopeptidases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D015544:Inositol 1,4,5-Trisphosphate; D008094:Lithium; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases