TY - JOUR
AU1 - Arnsten, A.
AB - Recent genetic and biochemical studies have also linked these illnesses to disinhibition of phosphotidyl inositol-protein kinase C signaling. For example, DAG kinase eta, an enzyme that metabolizes DAG and thus reduces protein kinase C activity, is the gene most altered in bipolar disorder. Similarly, regulator of G protein signaling 4 is the molecule most altered in the PFC of patients with schizophrenia, and this molecule normally serves to inhibit Gq signaling. Animal studies have shown that high levels of phosphotidyl inositol-protein kinase C signaling in the PFC markedly impair PFC function at the behavioral and cellular levels. Most importantly, many effective medications for bipolar disorder and schizophrenia inhibit phosphotidyl inositol-protein kinase C signaling, either through intracellular actions (lithium, valproate) or through extracellular blockade of receptors coupled to this pathway (5HT2 receptors and alpha-1 adrenoceptors). Recent data suggest that lithium and valproate can protect gray matter in patients with bipolar disorder. These findings encourage the development of protein kinase C inhibitors for the treatment of mental illness.
TI - Ameliorating prefrontal cortical dysfunction in mental illness: inhibition of phosphotidyl inositol-protein kinase C signaling
JF - Psychopharmacology
DO - 10.1007/s00213-008-1274-9
DA - 2009-01-01
UR - https://www.deepdyve.com/lp/springer-journals/ameliorating-prefrontal-cortical-dysfunction-in-mental-illness-wWbiOrIzgR
SP - 445
EP - 455
VL - 202
IS - 1
DP - DeepDyve
ER -