Activity-Dependent Neuroprotective Protein (ADNP): An Overview of Its Role in the Eye

Maugeri, Grazia; D’Amico, Agata Grazia; Magrì, Benedetta; Musumeci, Giuseppe; D’Agata, Velia

doi:10.3390/ijms232113654

Cited by 5 publications

(5 citation statements)

References 87 publications

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“…NAP derivatives have further shown neuroprotective activity (Amram et al, 2016; Brenneman et al, 2004; Gozes et al, 2014, 2014, 2016; Ivashko‐Pachima & Gozes, 2019; Ivashko‐Pachima, Seroogy, et al, 2021; Jouroukhin et al, 2012). Most recent work, addressing NAP as a neuroprotective agent, and complementing our own work, reviewed robust protective activity on the retina with ADNP children showing visual impairments (Van Dijck et al, 2019), and with further NAP protection against radiation (Maugeri, D'Amico, Giunta et al, 2022; Maugeri, D'Amico, Magri et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

A novel davunetide (NAPVSIPQQ to NAPVSIPQE) point mutation in activity‐dependent neuroprotective protein (ADNP) causes a mild developmental syndrome

Gozes

Shazman

2023

Eur J of Neuroscience

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NAP (NAPVSIPQ, drug candidate name, davunetide) is the neuroprotective fragment of activity-dependent neuroprotective protein (ADNP). Recent studies identified NAPVSIP as a Src homology 3 (SH3) domain-ligand association site, responsible for controlling signalling pathways regulating the cytoskeleton. Furthermore, the SIP motif in NAP/ADNP was identified as crucial for direct microtubule end-binding protein interaction facilitating microtubule dynamics and Tau microtubule interaction, at the microtubule end-binding protein site EB1 and EB3. Most de novo ADNP mutations reveal heterozygous STOP or frameshift STOP aberrations, driving the autistic/intellectual disability-related ADNP syndrome. Here, we report for the first time on a de novo missense mutation, resulting in ADNP containing NAPVISPQE instead of NAPVSIPQQ, in a child presenting developmental hypotonia, possibly associated with inflammation affecting food intake in early life coupled with fear of peer interactions and suggestive of a novel case of the ADNP syndrome. In silico modelling showed that the mutation Q (polar side chain) to E (negative side chain) affected the electrostatic characteristics of ADNP (reducing, while scattering the electrostatic positive patch). Comparison with the most prevalent pathogenic ADNP mutation, p.Tyr719*, indicated a further reduction in the electrostatic patch. Previously, exogenous NAP partially ameliorated deficits associated with ADNP p.Tyr719* mutations in transfected cells and in CRISPR/Cas9 genome edited cell and mouse models. These findings stress the importance of the NAP sequence in ADNP and as a future putative therapy for the ADNP syndrome.

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Section: Introductionmentioning

confidence: 99%

A novel davunetide (NAPVSIPQQ to NAPVSIPQE) point mutation in activity‐dependent neuroprotective protein (ADNP) causes a mild developmental syndrome

Gozes

Shazman

2023

Eur J of Neuroscience

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“…Therefore, it will be important to analyze the role of NAP on APCs, since these could represent a key target in the management of hyperglycemia-induced corneal epithelial inflammation. In light of the protective effects performed by NAP in the cornea, and given that treatment with this peptide exerted beneficial effects in in vitro and in vivo models of diabetes, it is desirable to test NAP or its analogue as a treatment for DK [163,185].…”

Section: Discussionmentioning

confidence: 99%

“…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].…”

Section: Activity-dependent Neuroprotective Protein (Adnp)mentioning

confidence: 99%

Involvement of Vasoactive Intestinal Peptide Family Members in Diabetic Keratopathy

Maugeri,

D’Amico,

Magrì

et al. 2024

Applied Sciences

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Diabetic keratopathy (DK) is a common ocular complication of diabetes, characterized by alteration of the normal wound-healing mechanism, reduction of epithelial hemidesmosomes, disruption of the basement membrane, impaired barrier function, reduced corneal sensitivity, corneal ulcers, and corneal edema. The limited number of clinical studies do not allow a full characterization of the pathophysiology of DK and, until now, effective therapeutic approaches have not been available. However, in recent years, neuropeptides gained great attention for their biochemical characteristics and therapeutic potential. This review focuses on the role of neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) in the eye and, in particular, in the cornea, in physiological conditions, or during DK, by providing an overview of this diabetes mellitus complication.

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“…Activity-dependent protein (ADNP) is a neuroprotective protein whose gene was discovered in 1999 by Bassan et al [18]. The peptide was found in nervous systems and different organs [19,20]. In fact, ADNP is indispensable for brain formation [21] and, through the interaction with nuclear chromatin, regulates the transcription of several genes linked to autophagy, axonal transport, embryogenesis, dendritic spine plasticity, and autism-linked protein translation [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Moderate Physical Activity Increases the Expression of ADNP in Rat Brain

Maugeri,

D’Amico,

Federico

et al. 2024

IJMS

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Activity-dependent neuroprotective protein (ADNP) is a neuroprotective protein essential for embryonic development, proper brain development, and neuronal plasticity. Its mutation causes the autism-like ADNP syndrome (also called the Helsmoortel-Van der Aa syndrome), characterized by neural developmental disorders and motor dysfunctions. Similar to the ADNP syndrome, the ADNP haploinsufficient mouse shows low synapse density, leading to motor and cognitive ability delays. Moderate physical activity (PA) has several neuroprotective and cognitive benefits, promoting neuronal survival, differentiation, neurogenesis, and plasticity. Until now, no study has investigated the effect of moderate exercise on ADNP expression and distribution in the rat brain. The aim of the current investigation was to study the effects of moderate exercise on the ADNP expression and neuronal activation measured by the microtubule protein β-Tubulin III. In pursuit of this objective, twenty-four rats were selected and evenly distributed into two categories: sedentary control rats and rats exposed to moderate physical activity on a treadmill over a span of 12 weeks. Our results showed that moderate PA increases the expression of ADNP and β-Tubulin III in the dentate gyrus (DG) hippocampal region and cerebellum. Moreover, we found a co-localization of ADNP and β-Tubulin III in both DG and cerebellum, suggesting a direct association of ADNP with adult neuronal activation induced by moderate PA.

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Activity-Dependent Neuroprotective Protein (ADNP): An Overview of Its Role in the Eye

Cited by 5 publications

References 87 publications

A novel davunetide (NAPVSIPQQ to NAPVSIPQE) point mutation in activity‐dependent neuroprotective protein (ADNP) causes a mild developmental syndrome

A novel davunetide (NAPVSIPQQ to NAPVSIPQE) point mutation in activity‐dependent neuroprotective protein (ADNP) causes a mild developmental syndrome

Involvement of Vasoactive Intestinal Peptide Family Members in Diabetic Keratopathy

Moderate Physical Activity Increases the Expression of ADNP in Rat Brain

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