Novel Evolutionary-conserved Role for the Activity-dependent Neuroprotective Protein (ADNP) Family That Is Important for Erythropoiesis

Dresner, Efrat; Malishkevich, Anna; Arviv, Carmit; Barak, Shelly Leibman; Alon, Shahar; Ofir, Rivka; Gothilf, Yoav; Gozes, Illana

doi:10.1074/jbc.m112.387027

Cited by 43 publications

(38 citation statements)

References 48 publications

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“…ADNP contains nine zinc finger domains and a homeobox domain (Dresner et al, 2012), suggesting that Somatosensory cortex (layer II/III) immunostained for ADNP (RB a-ADNP 1:000, Bethyl laboratories, TX, Catalog #IHC-00118) following (A) saline or (B) 5 mg/kg ketamine pre-treatment followed by 20 mg/kg ketamine treatment. (C) Fasciola cinereum.…”

Section: Low Concentrations Of Ketamine Increase the Protein Levels Amentioning

confidence: 99%

In vivo and in vitro ketamine exposure exhibits a dose-dependent induction of activity-dependent neuroprotective protein in rat neurons

et al. 2015

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Section: Low Concentrations Of Ketamine Increase the Protein Levels Amentioning

confidence: 99%

In vivo and in vitro ketamine exposure exhibits a dose-dependent induction of activity-dependent neuroprotective protein in rat neurons

et al. 2015

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“…ADNP2 is important for cellular protection [20]. In healthy conditions, ADNP mRNA levels correlate well with ADNP2 mRNA levels [21, 22]. Furthermore, peripheral ADNP2 mRNA levels (unlike ADNP mRNA levels) may change as a consequence of drug treatment, as seen in rats subjected to clozapine treatment [23].…”

Section: Introductionmentioning

confidence: 99%

Blood-Borne Activity-Dependent Neuroprotective Protein (ADNP) is Correlated with Premorbid Intelligence, Clinical Stage, and Alzheimer’s Disease Biomarkers

Malishkevich

Marshall

Schultz

et al. 2016

JAD

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Biomarkers for Alzheimer’s disease (AD) are vital for disease detection in the clinical setting. Discovered in our laboratory, activity-dependent neuroprotective protein (ADNP) is essential for brain formation and linked to cognitive functions. Here, we revealed that blood borne expression of ADNP and its paralog ADNP2 is correlated with premorbid intelligence, AD pathology, and clinical stage. Age adjustment showed significant associations between: 1] higher premorbid intelligence and greater serum ADNP, and 2] greater cortical amyloid and lower ADNP and ADNP2 mRNAs. Significant increases in ADNP mRNA levels were observed in patients ranging from mild cognitive impairment (MCI) to AD dementia. ADNP2 transcripts showed high correlation with ADNP transcripts, especially in AD dementia lymphocytes. ADNP plasma/serum and lymphocyte mRNA levels discriminated well between cognitively normal elderly, MCI, and AD dementia participants. Measuring ADNP blood-borne levels could bring us a step closer to effectively screening and tracking AD.

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“…During early somitogenesis, the expression of both genes re-appeared along the dorsal midline, and by 24 hpf was gradually refined to head and gut regions (Supplementary Fig. 8a) 30 . After 72h, adnpa expression restricted to the forebrain, the midbrain, the mid-hindbrain boundary and eye area (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

ADNP promotes neural differentiation by modulating Wnt/β-catenin signaling

Sun

Peng

Cao

et al. 2019

Preprint

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5 ADNP (Activity Dependent Neuroprotective Protein) is proposed as a neuroprotective 6 protein whose aberrant expression has been frequently linked to neural developmental 7 disorders, including the Helsmoortel-Van der Aa syndrome. However, its role in 8 neural development and pathology remains unclear. Using mESC (mouse embryonic 9 stem cell) directional neural differentiation as a model, we show that ADNP is 10 required for ESC neural induction and neuronal differentiation by maintaining Wnt 11 signaling. Mechanistically, ADNP functions to maintain the proper protein levels of 12 β-Catenin through binding to its armadillo domain which prevents its association with 13 key components of the degradation complex: Axin and APC. Loss of ADNP promotes 14 the formation of the degradation complex and hyperphosphorylation of β-Catenin by 15 GSK3β and subsequent degradation via ubiquitin-proteasome pathway, resulting in 16 down-regulation of key neuroectoderm developmental genes. We further show that 17 ADNP plays key role in cerebellar neuron formation. Finally, adnp gene disruption in 18 zebrafish embryos recapitulates key features of the mouse phenotype, including the 19 reduced Wnt signaling, defective embryonic cerebral neuron formation and the 20 massive neuron death. Thus, our work provides important insights into the role of 21 ADNP in neural development and the pathology of the Helsmoortel-Van der Aa 22 syndrome caused by ADNP gene mutation. 23 24 42 of mouse embryos. 43 De novo mutations in ADNP gene have recently been linked to neural 44 developmental disorders, including the Helsmoortel-Van der Aa syndrome 6 . Patients 45 display multiple symptoms, usually manifesting in early childhood with features such 46 as intellectual disability, facial dysmorphism, motor dysfunction and developmental 47 65 development which would be useful for understanding the pathology of the 66 Helsmoortel-Van der Aa syndrome caused by ADNP mutation. 67 . 68 69 70 Results 71Generation and characterization of Adnp-/-ESCs. To understand the molecular 72 function of ADNP, we generated Adnp mutant ESCs by using CRISPR/Cas9 73 technology. gRNAs were designed to target the 3' end of exon 4 of mouse Adnp gene 74 ( Fig. 1a). We have successfully generated 2 Adnp mutant alleles (-4 and -5 bp), 75 revealed by DNA genotyping around the CRISPR targeting site ( Fig. 1b). ADNP 76 protein was hardly detectable in Adnp-/-ESCs by Western blot using ADNP 77 antibodies from different resources ( Fig. 1c), which strongly indicated that the mutant 78 alleles are functional nulls. 79 In the traditional self-renewal medium containing LIF-KSR plus FBS, the newly 80 established Adnp-/-ESC colonies overall exhibited typical ESC-like morphology (Fig. 81 1d). To understand how loss of Adnp affected the global gene expression, we 82 performed RNA-sequencing (RNA-seq) experiments for control and early passaged 83Adnp-/-ESCs. Our RNA-seq analysis showed that the primitive endoderm genes such 84 as Gata6, Gata4, Sox17, Sox7 and Sparc were slightly up-regul...

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Novel Evolutionary-conserved Role for the Activity-dependent Neuroprotective Protein (ADNP) Family That Is Important for Erythropoiesis

Cited by 43 publications

References 48 publications

In vivo and in vitro ketamine exposure exhibits a dose-dependent induction of activity-dependent neuroprotective protein in rat neurons

In vivo and in vitro ketamine exposure exhibits a dose-dependent induction of activity-dependent neuroprotective protein in rat neurons

Blood-Borne Activity-Dependent Neuroprotective Protein (ADNP) is Correlated with Premorbid Intelligence, Clinical Stage, and Alzheimer’s Disease Biomarkers

ADNP promotes neural differentiation by modulating Wnt/β-catenin signaling

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