title: A role for the PKC signaling system in the pathophysiology and treatment of mood disorders: involvement of a functional imbalance?
abstract: Mood disorders, such as bipolar and major depressive disorders, are frequent, severe, and often disabling neuropsychiatric diseases affecting millions of individuals worldwide. Available mood stabilizers and antidepressants remain unsatisfactory because of their delayed and partial therapeutic efficacy. Therefore, the development of targeted therapies, working more rapidly and being fully effective, is urgently needed. In this context, the protein kinase C (PKC) signaling system, which regulates multiple neuronal processes implicated in mood regulation, can constitute a novel therapeutic target. This paper reviews the currently available knowledge regarding the role of the PKC signaling pathway in the pathophysiology of mood disorders and the therapeutic potential of PKC modulators. Current antidepressants and mood stabilizers have been shown to modulate the PKC pathway, and the inhibition of this intracellular signaling cascade results in antimanic-like properties in animal models. Disrupted PKC activity has been found both in postmortem brains and platelet from patients with mood disorders. Finally, the PKC inhibitor tamoxifen has recently demonstrated potent antimanic properties in several clinical trials. Overall, emerging data from preclinical and clinical research suggest an imbalance of the PKC signaling system in mood disorders. Thus, PKC may be a critical molecular target for the development of innovative therapeutics.
authors: Laboratoire de Neuropsychopharmacologie, Université Lyon 1, 8 avenue Rockefeller, 69373 Lyon Cedex 08, France. erika.abrial@univ-lyon1.fr
authors: Erika
authors: E
authors: Abrial
authors: Guillaume
authors: G
authors: Lucas
authors: Hélène
authors: H
authors: Scarna
authors: Nasser
authors: N
authors: Haddjeri
authors: Laura
authors: L
authors: Lambás-Señas
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D018692:Antimanic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001519:Behavior / Q000187:drug effects; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D019964:Mood Disorders / Q000188:drug therapy* / Q000503:physiopathology*; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D000928:Antidepressive Agents; D018692:Antimanic Agents; D007527:Isoenzymes; D011493:Protein Kinase C