Activity-dependent neuroprotective protein: a novel gene essential for brain formation

Pinhasov, Albert; Mandel, Shmuel; Torchinsky, Arkady; Giladi, Eliezer; Pittel, Zipora; Goldsweig, Andrew M.; Servoss, Stephen J.; Brenneman, Douglas E.; Gozes, Illana

doi:10.1016/s0165-3806(03)00162-7

Cited by 224 publications

(217 citation statements)

References 27 publications

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“…As indicated previously, ADNP has a role in the developing fetal mouse brain, and is associated with the activation of vital genes (Pinhasov et al, 2003). Colocalization of ADNP-like immunoreactivity with tubulin-like immunoreactivity (but not with actin microfilaments) was observed in selected astrocyte populations.…”

Section: Discussionsupporting

confidence: 62%

“…Furthermore, ADNP-like immunoreactivity was identified in conditioned media from astrocytes, and the concentration increased after treatment with VIP. Previous studies utilizing antibodies directed against other epitopes of ADNP have detected a protein of a similar molecular weight in cancer cells (Zamostiano et al, 2001) and in developing mouse embryos (Pinhasov et al, 2003). The subcellular localization of the protein indicated that it might be directed to different pathways in the cell, with the largest concentration directed to the nucleus.…”

Section: Discussionmentioning

confidence: 94%

“…ADNP-knockout mouse embryos do not survive beyond embryonic day 9.5. In ADNP-knockout embryos, the expression of Pax6, which is essential for formation of the cerebral cortex, is abolished in the brain primordial tissue and the cranial neural tube fails to close (Pinhasov et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Subcellular localization and secretion of activity-dependent neuroprotective protein in astrocytes

et al. 2004

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Activity-dependent neuroprotective protein (ADNP, ∼123562.8 Da), is synthesized in astrocytes and expression of ADNP mRNA is regulated by the neuroprotective peptide vasoactive intestinal peptide (VIP). The gene that encodes ADNP is conserved in human, rat and mouse, and contains a homeobox domain profile that includes a nuclear-export signal and a nuclear-localization signal. ADNP is essential for embryonic brain development, and NAP, an eight-amino acid peptide that is derived from ADNP, confers potent neuroprotection. Here, we investigate the subcellular localization of ADNP through cell fractionation, gel electrophoresis, immunoblotting and immunocytochemistry using α-CNAP, an antibody directed to the neuroprotective NAP fragment that constitutes part of an N-terminal epitope of ADNP. Recombinant ADNP was used as a competitive ligand to measure antibody specificity. ADNP-like immunoreactivity was found in the nuclear cell fraction of astrocytes and in the cytoplasm. In the cytoplasm, ADNP-like immunoreactivity colocalized with tubulin-like immunoreactivity and with microtubular structures, but not with actin microfilaments. Because microtubules are key components of developing neurons and brain, possible interaction between tubulin and ADNP might indicate a functional correlate to the role of ADNP in the brain. In addition, ADNP-like immunoreactivity in the extracellular milieu of astrocytes increased by ∼1.4 fold after incubation of the astrocytes with VIP. VIP is known to cause astrocytes to secrete neuroprotective/ neurotrophic factors, and we suggest that ADNP constitutes part of this VIP-stimulated protective milieu.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 94%

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Subcellular localization and secretion of activity-dependent neuroprotective protein in astrocytes

et al. 2004

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“…Discovered in our laboratory [19,20], ADNP is essential for brain formation [21], and ADNP deficits in mice results in tau pathology coupled to cognitive impairments [22]. In this respect, de novo, mostly truncating mutations in ADNP lead to cognitive impairments and autism in children [23][24][25][26].…”

Section: Blood Biomarkersmentioning

confidence: 99%

Specific protein biomarker patterns for Alzheimer’s disease: improved diagnostics in progress

Gozes

2017

EPMA Journal

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This short review looks at Alzheimer's disease (AD) diagnosis through my own point of view, going from imaging through cerebrospinal fluid to blood proteins. Over the last couple of years, we have published two papers targeted at Alzheimer's diagnosis. In one paper, we took an approach of selecting a specific target, namely, activitydependent neuroprotective protein (ADNP), and our results tightened the association of ADNP blood expression with intelligence. In another paper, we took an unbiased approach of analysis of all genes expressed in lymphoblastoid cells lines and discovered changes in expression of the regulator of G-protein signaling 2 (RGS2) as a potential AD predictor. This review will assess our data in comparison to selected independent studies focusing on blood protein biomarkers as well as assessing saliva and urine samples with potential predictive value for AD. Furthermore, the review will provide directions for a combination of innovative markers, stratifying the population toward disease prevention and personalized medicine.

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“…It is a peptide snippet from the activity-dependent neuroprotective protein (ADNP), [1], a protein essential for brain formation [20,24] recently found to be mutated in autism [10], deregulated in schizophrenia [5,21] and in patients with Alzheimer's disease [29]. In this respect, multiple preclinical evaluations, as well as clinical trials with NAP (davunetide) showed efficacy of the peptide [18,19].…”

Section: Introductionmentioning

confidence: 99%

Study of NAP adsorption and assembly on the surface of HOPG

et al. 2014

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Activity-dependent neuroprotective protein: a novel gene essential for brain formation

Cited by 224 publications

References 27 publications

Subcellular localization and secretion of activity-dependent neuroprotective protein in astrocytes

Subcellular localization and secretion of activity-dependent neuroprotective protein in astrocytes

Specific protein biomarker patterns for Alzheimer’s disease: improved diagnostics in progress

Study of NAP adsorption and assembly on the surface of HOPG

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