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.

Influence of TFAP2B and KCTD15 genetic variability on personality dimensions in anorexia and bulimia nervosa

“…These personality features are expressed by the involvement of a pattern of neuronal adaptations induced by central genes such as dopamine or serotonin, which has been consistently associated with ED‐coupled personality dimensions (Gervasini & Gamero‐Villarroel, 2015). Dopaminergic and serotonergic genes in the midbrain have AP‐2 binding sites; therefore it is likely that these transcription factors, aside from its established role during development, can also influence mood and personality in adults through this neurotransmitter system (Damberg, 2005; Damberg et al., 2001). In the same manner, variability in the KCTD15 locus could play its role by altering TFAP2B post‐translational modifications leading to orexigenic signaling and consummatory behavior, as shown in Figure 1.…”

Association between Serotonin Transporter-Linked Polymorphic Region and Escitalopram Antidepressant Treatment Response in Korean Patients with Major Depressive Disorder

“…A number of polymorphisms have been found in the proximity of the insertion/deletion locus, such as rs25531, rs25532, rs2020933 and a 17-bp variable tandem repeat in the second intron (STin2) [50,51,52,53], and have been proposed to modulate the functionality of 5-HTTLPR [3]. The rs25531, which is located in the sixth repeat of the 5-HTTLPR outside the deleted segment [3], can co-occur with either the long or short variant of the 5-HTTLPR [9].…”

Genetic aspects of binge eating disorder Part 2. Molecular genetics and pharmacogenetic approaches

“…: fatty acid amide hydrolase, FAAH), главного фермента деградации эндоканнабиноидов, вовлеченных как в механизмы ад-дикции, так и в регуляцию пищевого поведения, оказался связанным с ожирением, но не с ВЕD [52]. Возможна роль генетических вариантов, связанных с системами регуля-обзоры ции экспрессии генов, прежде всего различных транс-крипционных факторов, например имеются данные о возможной связи гена транскрипционного фактора АР2μ с ВЕD [53].…”