Chromatin remodeler Activity-Dependent Neuroprotective Protein (ADNP) contributes to syndromic autism

Abstract

Background Individuals affected with autism often suffer additional co-morbidities such as intellectual disability. The genes contributing to autism cluster on a relatively limited number of cellular pathways, including chromatin remodeling. However, limited information is available on how mutations in single genes can result in such pleiotropic clinical features in affected individuals. In this review, we summarize available information on one of the most frequently mutated genes in syndromic autism the Activity-Dependent Neuroprotective Protein (ADNP). Results Heterozygous and predicted loss-of-function ADNP mutations in individuals inevitably result in the clinical presentation with the Helsmoortel–Van der Aa syndrome, a frequent form of syndromic autism. ADNP, a zinc finger DNA-binding protein has a role in chromatin remodeling: The protein is associated with the pericentromeric protein HP1, the SWI/SNF core complex protein BRG1, and other members of this chromatin remodeling complex and, in murine stem cells, with the chromodomain helicase CHD4 in a ChAHP complex. ADNP has recently been shown to possess R-loop processing activity. In addition, many additional functions, for instance, in association with cytoskeletal proteins have been linked to ADNP. Conclusions We here present an integrated evaluation of all current aspects of gene function and evaluate how abnormalities in chromatin remodeling might relate to the pleiotropic clinical presentation in individual“s” with Helsmoortel–Van der Aa syndrome.

Moderate Physical Activity Increases the Expression of ADNP in Rat Brain

“…It modulates several key genes linked to synaptic transmissions, such as ion channels, tubulin and microtubules, and genes regulating the autophagic process [43][44][45]. When one of the two copies of the ADNP gene is mutated and loses its normal function, the ADNP syndrome occurs, characterized by intellectual disability and global developmental delay which includes both language and motor domains [46]. In the present paper, we demonstrated for the first time that moderate PA significantly increased the expression of ADNP in the DG area of the hippocampus as compared to sedentary rats, whose DG cells did not always show strong immunopositivity staining for ADNP.…”

Putative Role of the Futile Repair Initiated by Human Thymine-DNA Glycosylase in Formation of Programmed Strand Breaks in Neuronal Enhancers

“…To check the possible involvement of TDG in formation C to T and T to C transitions in ADNP gene [17], we constructed oligonucleotide duplexes containing T at position 17 for substrate named C>T-ADNP/c.C>T-ADNP and C at the same position for substrate named ADNP-T>C/c.ADNP-T>C. Even after incubation for 18 h in the presence of TDG, no significant excision of T and C at the indicated positions was observed, as can be seen in Fig. 5, where the 16-mer fragments at lanes 6 and 21 were excised by only 1.4 % and 0.25 %, respectively.…”

Involvement of Vasoactive Intestinal Peptide Family Members in Diabetic Keratopathy

“…ADNP is expressed in different tissues and organs of the body with the highest expression in the human brain, gastrointestinal system, respiratory, and reproductive system (Figure 4) [161]. The expression of ADNP was also detected in the eye, particularly in the retina and cornea [51,162,163].…”