{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:06:32Z","timestamp":1790805992776,"version":"4.1.0"},"reference-count":100,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"NIMH","doi-asserted-by":"publisher","award":["R21MH132839"],"award-info":[{"award-number":["R21MH132839"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R21MH132839"],"award-info":[{"award-number":["R21MH132839"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense, Congressionally Directed Medical Research Programs (CDMRP), Autism Program e","doi-asserted-by":"publisher","award":["AR220067"],"award-info":[{"award-number":["AR220067"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"award":["AR220067"],"award-info":[{"award-number":["AR220067"]}],"id":[{"id":"https:\/\/ror.org\/03g2zjp07","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The Activity-Dependent Neuroprotective Protein (ADNP) is an important regulator of early brain development, especially during cortical neurogenesis and neurite formation. De novo point mutations or haploinsufficiency of the ADNP gene result in ADNP syndrome, which is also known as Helsmoortel-Van der Aa syndrome, a complex neurodevelopmental disorder recognized as a leading single-gene cause of syndromic autism spectrum disorder (ASD) and intellectual disability. ADNP works as both a transcription factor and a microtubule (MT) regulator. As a transcription factor, ADNP is a key component of chromatin remodeling complexes such as ChAHP (CHD4 (Chromodomain Helicase DNA-binding Protein 4)-ADNP-HP1 (Heterochromatin Protein 1)) and SWI\/SNF (Switch\/Sucrose Non-Fermentable), and it tightly regulates the expression of numerous essential developmental genes. ADNP also modulates the Wnt\/\u03b2-catenin signaling pathway. During neural differentiation, ADNP is redistributed from the nucleus to the cytoplasm, and this redistribution is regulated by binding to 14-3-3 proteins, which are phosphorylated by protein Kinase C (PKC). After relocating to the cytoplasm, ADNP functions as an MT regulator by binding to microtubule end-binding proteins (EB1 and EB3) and Tau to control neurite formation. Previous studies have focused on NAP (also known as Davunetide, a peptide derived from ADNP) in MT regulation and its therapeutic potential for autism spectrum disorder (ASD) and neurodegenerative diseases, such as Alzheimer\u2019s disease. This review highlights the functions of full-length ADNP and NAP in early brain development, particularly in neurogenesis and neurite formation during cortical development. We will also discuss the potential of NAP as a therapeutic medication for neurodevelopmental disorders, especially ASD and ADNP syndrome.<\/jats:p>","DOI":"10.3390\/ijms27136085","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T13:19:31Z","timestamp":1783430371000},"page":"6085","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["ADNP Functions During Early Brain Development and Their Relevance to ASD and ADNP Syndrome"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3181-8310","authenticated-orcid":false,"given":"Xiaonan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5227-7517","authenticated-orcid":false,"given":"Shiena","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2267-9723","authenticated-orcid":false,"given":"Sierra","family":"Coleman","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicky","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Telfer","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasu D.","family":"Kansagra","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilit","family":"Drak","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laasya Reddy","family":"Pesaladinne","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samridhi","family":"Sudan","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anushka","family":"Singhal","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0173-0430","authenticated-orcid":false,"given":"Kazuhito","family":"Toyo-oka","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.ceb.2008.09.008","article-title":"The cell biology of neural stem and progenitor cells and its significance for their proliferation versus differentiation during mammalian brain development","volume":"20","author":"Farkas","year":"2008","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Belmonte-Mateos, C., and Pujades, C. (2021). From Cell States to Cell Fates: How Cell Proliferation and Neuronal Differentiation Are Coordinated During Embryonic Development. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.781160"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1111\/jnc.14338","article-title":"Cortical progenitor biology: Key features mediating proliferation versus differentiation","volume":"146","author":"Uzquiano","year":"2018","journal-title":"J. Neurochem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"65","DOI":"10.31887\/DCNS.2020.22.1\/macrocq","article-title":"Neurodevelopmental disorders\u2014The history and future of a diagnostic concept","volume":"22","author":"Crocq","year":"2020","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1038\/s41380-022-01939-3","article-title":"The cytoplasmic localization of ADNP through 14-3-3 promotes sex-dependent neuronal morphogenesis, cortical connectivity, and calcium signaling","volume":"28","author":"Bennison","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0165-3806(03)00162-7","article-title":"Activity-dependent neuroprotective protein: A novel gene essential for brain formation","volume":"144","author":"Pinhasov","year":"2003","journal-title":"Dev. Brain Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.biopsych.2018.02.1173","article-title":"Clinical Presentation of a Complex Neurodevelopmental Disorder Caused by Mutations in ADNP","volume":"85","author":"Cappuyns","year":"2019","journal-title":"Biol. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/ajmg.c.31413","article-title":"The transcriptional regulator ADNP links the BAF (SWI\/SNF) complexes with autism","volume":"166","author":"Vandeweyer","year":"2014","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/ng.2899","article-title":"A SWI\/SNF-related autism syndrome caused by de novo mutations in ADNP","volume":"46","author":"Helsmoortel","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1002\/aur.1980","article-title":"The autism spectrum phenotype in ADNP syndrome","volume":"11","author":"Arnett","year":"2018","journal-title":"Autism Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1043","DOI":"10.1038\/tp.2017.27","article-title":"Premature primary tooth eruption in cognitive\/motor-delayed ADNP-mutated children","volume":"7","author":"Gozes","year":"2017","journal-title":"Transl. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e2405981122","DOI":"10.1073\/pnas.2405981122","article-title":"The chromatin remodeler ADNP regulates neurodevelopmental disorder risk genes and neocortical neurogenesis","volume":"122","author":"Larrigan","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"34448","DOI":"10.1074\/jbc.M704756200","article-title":"Activity-dependent neuroprotective protein constitutes a novel element in the SWI\/SNF chromatin remodeling complex","volume":"282","author":"Mandel","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2984","DOI":"10.1038\/s41467-020-16799-0","article-title":"ADNP promotes neural differentiation by modulating Wnt\/\u03b2-catenin signaling","volume":"11","author":"Sun","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4956","DOI":"10.1172\/JCI98199","article-title":"Activity-dependent neuroprotective protein deficiency models synaptic and developmental phenotypes of autism-like syndrome","volume":"128","author":"Sragovich","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1016\/j.peptides.2007.08.004","article-title":"NAP protects hippocampal neurons against multiple toxins","volume":"28","author":"Zemlyak","year":"2007","journal-title":"Peptides"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Oz, S., Ivashko-Pachima, Y., and Gozes, I. (2012). The ADNP derived peptide, NAP modulates the tubulin pool: Implication for neurotrophic and neuroprotective activities. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051458"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/j.1471-4159.2007.04761.x","article-title":"The peptide NAP promotes neuronal growth and differentiation through extracellular signal-regulated protein kinase and Akt pathways, and protects neurons co-cultured with astrocytes damaged by ethanol","volume":"103","author":"Pascual","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.3233\/JAD-2010-1335","article-title":"The neuroprotective peptide NAP does not directly affect polymerization or dynamics of reconstituted neural microtubules","volume":"19","author":"Yenjerla","year":"2010","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ganaiem, M., Gildor, N.D., Shazman, S., Karmon, G., Ivashko-Pachima, Y., and Gozes, I. (2023). NAP (Davunetide): The Neuroprotective ADNP Drug Candidate Penetrates Cell Nuclei Explaining Pleiotropic Mechanisms. Cells, 12.","DOI":"10.3390\/cells12182251"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Harutyunyan, L., D\u2019Incal, C.P., Jansen, A.C., Meuwissen, M., Van Dijck, A., and Kooy, R.F. (2025). A Systematic Review Illustrates the Expanding Clinical and Molecular Landscape of Helsmoortel-Van der Aa Syndrome. Brain Sci., 16.","DOI":"10.3390\/brainsci16010004"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Gozes, I. (2020). The ADNP Syndrome and CP201 (NAP) Potential and Hope. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.608444"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1038\/mp.2016.255","article-title":"ADNP\/NAP dramatically increase microtubule end-binding protein-Tau interaction: A novel avenue for protection against tauopathy","volume":"22","author":"Sayas","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.biopsych.2021.09.018","article-title":"Novel ADNP Syndrome Mice Reveal Dramatic Sex-Specific Peripheral Gene Expression with Brain Synaptic and Tau Pathologies","volume":"92","author":"Karmon","year":"2022","journal-title":"Biol. Psychiatry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100138","DOI":"10.1016\/j.xhgg.2022.100138","article-title":"An open-label study evaluating the safety, behavioral, and electrophysiological outcomes of low-dose ketamine in children with ADNP syndrome","volume":"3","author":"Kolevzon","year":"2022","journal-title":"Hum. Genet. Genom. Adv."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1046\/j.1471-4159.1999.0721283.x","article-title":"Complete sequence of a novel protein containing a femtomolar-activity-dependent neuroprotective peptide","volume":"72","author":"Bassan","year":"1999","journal-title":"J. Neurochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1074\/jbc.M007416200","article-title":"Cloning and characterization of the human activity-dependent neuroprotective protein","volume":"276","author":"Zamostiano","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13229-024-00584-7","article-title":"Clinical impact and in vitro characterization of ADNP variants in pediatric patients","volume":"15","author":"Ge","year":"2024","journal-title":"Mol. Autism"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13148-023-01450-8","article-title":"Chromatin remodeler Activity-Dependent Neuroprotective Protein (ADNP) contributes to syndromic autism","volume":"15","author":"Konings","year":"2023","journal-title":"Clin. Epigenet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s40478-024-01743-w","article-title":"ADNP dysregulates methylation and mitochondrial gene expression in the cerebellum of a Helsmoortel-Van der Aa syndrome autopsy case","volume":"12","author":"Ibrahim","year":"2024","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/s41586-018-0153-8","article-title":"Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes","volume":"557","author":"Ostapcuk","year":"2018","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1002\/aur.70132","article-title":"ADNP Exhibits Methyltransferase Activity in Overexpression Systems and Modulates DNA and Histone Methylation","volume":"18","author":"Cappuyns","year":"2025","journal-title":"Autism Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"106309","DOI":"10.1016\/j.ebiom.2026.106309","article-title":"An Adnp frameshift variant disrupts Wnt signalling inducing chromatocytoskeletal defects and autism-related behaviour in male mice","volume":"128","author":"Cappuyns","year":"2026","journal-title":"eBioMedicine"},{"key":"ref_34","first-page":"4325","article-title":"POU3F2 regulates canonical Wnt signalling via SOX13 and ADNP to expand the neural progenitor population","volume":"148","author":"Benoit","year":"2025","journal-title":"Brain"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3316","DOI":"10.1038\/s41380-022-01603-w","article-title":"SH3- and actin-binding domains connect ADNP and SHANK3, revealing a fundamental shared mechanism underlying autism","volume":"27","author":"Ganaiem","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4043","DOI":"10.1007\/s00018-014-1611-6","article-title":"A SxIP motif interaction at the microtubule plus end is important for processive retrograde axonal transport","volume":"71","author":"Kapur","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1016\/j.bpj.2021.03.004","article-title":"SxIP binding disrupts the constitutive homodimer interface of EB1 and stabilizes EB1 monomer","volume":"120","author":"Ayyappan","year":"2021","journal-title":"Biophys. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"RP98063","DOI":"10.7554\/eLife.98063.3","article-title":"Dock-and-lock binding of SxIP ligands is required for stable and selective EB1 interactions","volume":"13","author":"Almeida","year":"2025","journal-title":"eLife"},{"key":"ref_39","unstructured":"Ivashko-Pachima, Y., and Gozes, I. (2021). Activity-Dependent Neuroprotective Protein (ADNP)-End-Binding Protein (EB) Interactions Regulate Microtubule Dynamics Toward Protection Against Tauopathy, Elsevier. Progress in Molecular Biology and Translational Science."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1111\/j.1471-4159.2008.05522.x","article-title":"Regulation of neural progenitor cell development in the nervous system","volume":"106","author":"Corbin","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.neuron.2011.05.001","article-title":"Adult neurogenesis in the mammalian brain: Significant answers and significant questions","volume":"70","author":"Ming","year":"2011","journal-title":"Neuron"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Urban, N., and Guillemot, F. (2014). Neurogenesis in the embryonic and adult brain: Same regulators, different roles. Front. Cell. Neurosci., 8, Correction in Front. Cell. Neurosci. 2015, 9, 160.","DOI":"10.3389\/fncel.2014.00396"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.conb.2010.04.010","article-title":"Signaling in adult neurogenesis","volume":"20","author":"Mu","year":"2010","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Jiang, M., Jang, S.E., and Zeng, L. (2023). The Effects of Extrinsic and Intrinsic Factors on Neurogenesis. Cells, 12.","DOI":"10.3390\/cells12091285"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/(SICI)1097-4695(199808)36:2<287::AID-NEU13>3.0.CO;2-B","article-title":"Regulation of neurogenesis by growth factors and neurotransmitters","volume":"36","author":"Cameron","year":"1998","journal-title":"J. Neurobiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/j.1527-3458.2005.tb00053.x","article-title":"NAP: Research and development of a peptide derived from activity-dependent neuroprotective protein (ADNP)","volume":"11","author":"Gozes","year":"2005","journal-title":"CNS Drug Rev."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Sun, X., Yu, W., Li, L., and Sun, Y. (2020). ADNP Controls Gene Expression Through Local Chromatin Architecture by Association with BRG1 and CHD4. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00553"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"dev146589","DOI":"10.1242\/dev.146589","article-title":"Wnt signaling in development and tissue homeostasis","volume":"145","author":"Steinhart","year":"2018","journal-title":"Development"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.cell.2006.10.018","article-title":"Wnt\/\u03b2-catenin signaling in development and disease","volume":"127","author":"Clevers","year":"2006","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1038\/s41380-024-02879-w","article-title":"ADNP is essential for sex-dependent hippocampal neurogenesis, through male unfolded protein response and female mitochondrial gene regulation","volume":"30","author":"Shapira","year":"2024","journal-title":"Mol. Psychiatry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/j.cell.2019.08.007","article-title":"The ChAHP Complex Counteracts Chromatin Looping at CTCF Sites that Emerged from SINE Expansions in Mouse","volume":"178","author":"Kaaij","year":"2019","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Wulfridge, P., Rell, N., Doherty, J., Fang, K.C., Lynskey, M.L., and Sarma, K. (2026). ADNP regulates chromatin architecture and lineage fidelity during neural differentiation. PLoS Genet., 22.","DOI":"10.1371\/journal.pgen.1012081"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1167\/iovs.04-0766","article-title":"The peptides ADNF-9 and NAP increase survival and neurite outgrowth of rat retinal ganglion cells in vitro","volume":"46","author":"Lagreze","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.stem.2010.11.028","article-title":"Proliferative neural stem cells have high endogenous ROS levels that regulate self-renewal and neurogenesis in a PI3K\/Akt-dependant manner","volume":"8","author":"Orozco","year":"2011","journal-title":"Cell Stem Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3112","DOI":"10.1523\/JNEUROSCI.17-09-03112.1997","article-title":"Bax deficiency prevents the increased cell death of immature neurons in bcl-x-deficient mice","volume":"17","author":"Shindler","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1161\/01.STR.0000014207.05597.D7","article-title":"NAP, a femtomolar-acting peptide, protects the brain against ischemic injury by reducing apoptotic death","volume":"33","author":"Leker","year":"2002","journal-title":"Stroke"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1007\/s12031-012-9921-3","article-title":"Neurotrophic peptides, ADNF-9 and NAP, prevent alcohol-induced apoptosis at midgestation in fetal brains of C57BL\/6 mouse","volume":"49","author":"Sari","year":"2013","journal-title":"J. Mol. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"457.e1","DOI":"10.1016\/j.ajog.2010.03.050","article-title":"Prevention of the alcohol-induced changes in brain-derived neurotrophic factor expression using neuroprotective peptides in a model of fetal alcohol syndrome","volume":"202","author":"Incerti","year":"2010","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s12031-007-9013-y","article-title":"ADNP differential nucleus\/cytoplasm localization in neurons suggests multiple roles in neuronal differentiation and maintenance","volume":"35","author":"Mandel","year":"2008","journal-title":"J. Mol. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1186\/s13148-025-01998-7","article-title":"A frameshift variant in activity-dependent neuroprotective protein (ADNP) causes nucleocytoskeletal alterations in a dizygotic male twin: A case study","volume":"17","author":"Annear","year":"2025","journal-title":"Clin. Epigenet."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Ohtaka-Maruyama, C., and Okado, H. (2015). Molecular Pathways Underlying Projection Neuron Production and Migration during Cerebral Cortical Development. Front. Neurosci., 9, Correction in Front. Neurosci. 2016, 10, 160.","DOI":"10.3389\/fnins.2016.00160"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"kvac007","DOI":"10.1093\/oons\/kvac007","article-title":"Establishing neuronal polarity: Microtubule regulation during neurite initiation","volume":"1","author":"Higgs","year":"2022","journal-title":"Oxf. Open Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13229-026-00713-4","article-title":"ADNP missense variant p.C687R disrupts chromatin regulation and GABAergic differentiation in Helsmoortel-Van der Aa syndrome","volume":"17","author":"Chen","year":"2026","journal-title":"Mol. Autism"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/neu.10284","article-title":"Actin and microtubules in neurite initiation: Are MAPs the missing link?","volume":"58","author":"Dehmelt","year":"2004","journal-title":"J. Neurobiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1038\/ncb1654","article-title":"Filopodia are required for cortical neurite initiation","volume":"9","author":"Dent","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"86","DOI":"10.4161\/bioa.26259","article-title":"The cytoskeleton and neurite initiation","volume":"3","author":"Flynn","year":"2013","journal-title":"Bioarchitecture"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.neuron.2012.09.038","article-title":"ADF\/cofilin-mediated actin retrograde flow directs neurite formation in the developing brain","volume":"76","author":"Flynn","year":"2012","journal-title":"Neuron"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s00441-014-1955-0","article-title":"Cytoskeletal and signaling mechanisms of neurite formation","volume":"359","author":"Sainath","year":"2015","journal-title":"Cell Tissue Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e201800288","DOI":"10.26508\/lsa.201800288","article-title":"Opposing functions of F-BAR proteins in neuronal membrane protrusion, tubule formation, and neurite outgrowth","volume":"2","author":"Taylor","year":"2019","journal-title":"Life Sci. Alliance"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Lasser, M., Tiber, J., and Lowery, L.A. (2018). The Role of the Microtubule Cytoskeleton in Neurodevelopmental Disorders. Front. Cell. Neurosci., 12.","DOI":"10.3389\/fncel.2018.00165"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/mp.2013.174","article-title":"Autophagy has a key role in the pathophysiology of schizophrenia","volume":"20","author":"Malishkevich","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Ivashko-Pachima, Y., and Gozes, I. (2019). A Novel Microtubule-Tau Association Enhancer and Neuroprotective Drug Candidate: Ac-SKIP. Front. Cell. Neurosci., 13, Correction in Front. Cell. Neurosci. 2021, 15, 687301.","DOI":"10.3389\/fncel.2019.00435"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Ivashko-Pachima, Y., Maor-Nof, M., and Gozes, I. (2019). NAP (davunetide) preferential interaction with dynamic 3-repeat Tau explains differential protection in selected tauopathies. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0213666"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1385\/JMN:25:3:225","article-title":"Activity-dependent neurotrophic factor-9 and NAP promote neurite outgrowth in rat hippocampal and cortical cultures","volume":"25","author":"Gozes","year":"2005","journal-title":"J. Mol. Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"507","DOI":"10.2174\/156720507783018208","article-title":"NAP, a neuroprotective drug candidate in clinical trials, stimulates microtubule assembly in the living cell","volume":"4","author":"Gozes","year":"2007","journal-title":"Curr. Alzheimer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.biopsych.2019.08.020","article-title":"Neuroprotective Peptide NAPVSIPQ Antagonizes Ethanol Inhibition of L1 Adhesion by Promoting the Dissociation of L1 and Ankyrin-G","volume":"87","author":"Dou","year":"2020","journal-title":"Biol. Psychiatry"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"115573","DOI":"10.1016\/j.addr.2025.115573","article-title":"Intranasal NAP (Davunetide): Neuroprotection and circadian rhythmicity","volume":"220","author":"Galushkin","year":"2025","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1007\/s12031-020-01632-6","article-title":"Deciphering the Enigma: NAP (CP201) the Active ADNP Drug Candidate Enters Cells by Dynamin-Associated Endocytosis","volume":"70","author":"Gozes","year":"2020","journal-title":"J. Mol. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.npep.2013.10.011","article-title":"Microtubule-stabilizing peptides and small molecules protecting axonal transport and brain function: Focus on davunetide (NAP)","volume":"47","author":"Magen","year":"2013","journal-title":"Neuropeptides"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1124\/jpet.107.130526","article-title":"A neuronal microtubule-interacting agent, NAPVSIPQ, reduces tau pathology and enhances cognitive function in a mouse model of Alzheimer\u2019s disease","volume":"325","author":"Matsuoka","year":"2008","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/mp.2013.32","article-title":"NAP (davunetide) rescues neuronal dysfunction in a Drosophila model of tauopathy","volume":"18","author":"Quraishe","year":"2013","journal-title":"Mol. Psychiatry"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1038\/mp.2014.97","article-title":"The NAP motif of activity-dependent neuroprotective protein (ADNP) regulates dendritic spines through microtubule end binding proteins","volume":"19","author":"Oz","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"171488","DOI":"10.1016\/j.peptides.2026.171488","article-title":"Activity dependent neuroprotective protein mediates the protective effects against VEGF-induced corneal barrier disruption in diabetes","volume":"197","author":"Maugeri","year":"2026","journal-title":"Peptides"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1111\/j.1471-4159.2006.03936.x","article-title":"Peptide neuroprotection through specific interaction with brain tubulin","volume":"98","author":"Divinski","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Gozes, I., Ivashko-Pachima, Y., and Sayas, C.L. (2018). ADNP, a Microtubule Interacting Protein, Provides Neuroprotection Through End Binding Proteins and Tau: An Amplifier Effect. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00151"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.3233\/JAD-131664","article-title":"Novel tubulin and tau neuroprotective fragments sharing structural similarities with the drug candidate NAP (Davuentide)","volume":"40","author":"Gozes","year":"2014","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e168554","DOI":"10.1172\/JCI168554","article-title":"Disruption of axonal transport in neurodegeneration","volume":"133","author":"Berth","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1039\/D3MD00012E","article-title":"Microtubule stabilising peptides: New paradigm towards management of neuronal disorders","volume":"14","author":"Bhargava","year":"2023","journal-title":"RSC Med. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"656","DOI":"10.2174\/1871527320666210728144043","article-title":"Regulation of Microtubule: Current Concepts and Relevance to Neurodegenerative Diseases","volume":"21","author":"Ghosh","year":"2022","journal-title":"CNS Neurol. Disord.-Drug Targets"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nature13772","article-title":"Synaptic, transcriptional and chromatin genes disrupted in autism","volume":"515","author":"He","year":"2014","journal-title":"Nature"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"(2015). The Deciphering Developmental Disorders Study. Large-scale discovery of novel genetic causes of developmental disorders. Nature, 519, 223\u2013228.","DOI":"10.1038\/nature14135"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.cell.2019.12.036","article-title":"Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism","volume":"180","author":"Satterstrom","year":"2020","journal-title":"Cell"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1136\/jmedgenet-2014-102444","article-title":"Expansion of the clinical phenotype associated with mutations in activity-dependent neuroprotective protein","volume":"51","author":"Pescosolido","year":"2014","journal-title":"J. Med. Genet."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/s41588-022-01148-2","article-title":"Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate-risk genes","volume":"54","author":"Zhou","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.ajhg.2020.07.003","article-title":"Episignatures Stratifying Helsmoortel-Van Der Aa Syndrome Show Modest Correlation with Phenotype","volume":"107","author":"Breen","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/s41431-024-01556-4","article-title":"Loss-of-function of activity-dependent neuroprotective protein (ADNP) by a splice-acceptor site mutation causes Helsmoortel-Van der Aa syndrome","volume":"32","author":"Annear","year":"2024","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/s41398-025-03675-y","article-title":"Systemic davunetide provides sex-specific neuroprotection during Coronary Artery Bypass Grafting (CABG)","volume":"15","author":"Gozes","year":"2025","journal-title":"Transl. Psychiatry"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/s12031-025-02420-w","article-title":"The ADNP-Mediated Transcriptome Response to Ketamine Impairs the Cytoskeletal Protein Axis","volume":"75","author":"Mateiu","year":"2025","journal-title":"J. Mol. Neurosci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"138460","DOI":"10.1016\/j.neulet.2025.138460","article-title":"Everolimus ameliorates cognitive deficits and synaptic dysfunction in mice with prefrontal cortical ADNP knockdown","volume":"871","author":"Xiang","year":"2026","journal-title":"Neurosci. Lett."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1002\/aur.70069","article-title":"Synaptic Deficits in Adnp-Mutant Mice Are Ameliorated by Histone Demethylase LSD1 Inhibition","volume":"18","author":"Lin","year":"2025","journal-title":"Autism Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/6085\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T12:55:31Z","timestamp":1783515331000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/6085"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":100,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27136085"],"URL":"https:\/\/doi.org\/10.3390\/ijms27136085","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]}}}