Transcription factor AP-2 and monoaminergic functions in the central nervous system

Abstract

In the central nervous system, transcription factor AP-2 family is one of the critical regulatory factors for neural gene expression and neuronal development. Several genes in the monoaminergic systems display AP-2 binding sites in regulatory regions. In addition, brainstem levels of transcription factor AP-2alpha and AP-2beta are positively correlated to monoamine measures in rat forebrain, suggesting a regulatory role of AP-2 also in the adult brain. Great changes in psychiatric phenotypes due to genetic factors are seldom the result of a single gene polymorphism. Recently, identification of combinations of candidate genes that are all linked to one disease or psychiatric phenotype has been discussed. The expression of these candidate genes might be regulated by the same transcription factors, e.g. AP-2. Recent data on transcription factor AP-2 family in relation to monoaminergic functions are described in this paper. Transcription factor AP-2beta genotype has been studied in relation to personality, platelet monoamine oxidase (MAO) activity, CSF-levels of monoamine metabolites, binge-eating disorder, premenstrual dysphoric disorder, and schizophrenia. Furthermore, the involvement of AP-2 in the molecular mechanism of antidepressant drugs is discussed. Altogether, this paper discusses data supporting a notion that the transcription factor AP-2 family is involved in the regulation of the monoaminergic systems both pre- and postnatally, and, therefore, might be involved in the pathophysiology of neuropsychiatric disorders.