Neurotrophic signaling cascades in the pathophysiology and treatment of bipolar disorder.
Increasing evidence suggests that bipolar disorder (BPD) is associated with regional brain volumetric reductions, accompanied by cellular atrophy and/or loss. Considerable data suggest that the protypical drugs for BPD--lithium and valproate--when administered in therapeutically relevant paradigms regulate neurotrophic signaling cascades. Notably, brain-derived neurotrophic factor, the extracellular signal-regulated kinase pathway, the glycogen synthase kinase-3-mediated pathway and Bcl-2 are major targets for mood stabilizers. Further data suggest that agents which directly target neurotrophic signaling cascades may have considerable utility for the treatment of this devastating illness.
Shaltiel
Galit
G
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-4405, USA.
Chen
Guang
G
Manji
Husseini K
HK
D000818:Animals; D001714:Bipolar Disorder / Q000378:metabolism* / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction
D019208:Brain-Derived Neurotrophic Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D048049:Extracellular Signal-Regulated MAP Kinases; D038362:Glycogen Synthase Kinase 3