The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Activity-Dependent Neuroprotective Protein Snippet NAP Reduces Tau Hyperphosphorylation and Enhances Learning in a Novel Transgenic Mouse Model
Abstract
Activity-dependent neuroprotective protein (ADNP) differentially interacts with chromatin to regulate essential genes. Because complete ADNP deficiency is embryonic lethal, the outcome of partial ADNP deficiency was examined. ADNP(+/-) mice exhibited cognitive deficits, significant increases in phosphorylated tau, tangle-like structures, and neurodegeneration compared with ADNP(+/+) mice. Increased tau hyperphosphorylation is known to cause memory impairments in neurodegenerative diseases associated with tauopathies, including the most prevalent Alzheimer's disease. The current results suggest that ADNP is an essential protein for brain function and plays a role in normal cognitive performance. ADNP-deficient mice offer an ideal paradigm for evaluation of cognitive enhancers. NAP (NAPVSIPQ) is a peptide derived from ADNP that interacts with microtubules and provides potent neuroprotection. NAP treatment partially ameliorated cognitive deficits and reduced tau hyperphosphorylation in the ADNP(+/-) mice. NAP is currently in phase II clinical trials assessing effects on mild cognitive impairment.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“while ADNP+/- mice show tauopathy, neuronal cell death and abnormalities in social behaviour and cognitive functioning18,34.”
From A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP (2014) · cites this paper as [18]
In the citing paper
“Of the other genes reported as differentially expressed in Adnp-/-23 and Adnp+/-18 mice (down: CCNC, TMPO, PLAGL2; up: ABCF3), only PLAGL2 was found to be differentially regulated in our patients (Supplementary Fig. 3e).”
From A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP (2014) · cites this paper as [18]
Citations
Cites
Grundman, M. (2004) · Archives of Neurology · doi:10.1001/archneur.61.1.59 · Cited by 972
Roles of Pax-genes in developing and adult brain as suggested by expression patterns
Stoykova, A., & Gruss, P. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-03-01395.1994 · Cited by 577
Kinases and phosphatases and tau sites involved in Alzheimer neurofibrillary degeneration
Wang, J., Grundke, I., & Iqbal, K. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05226.x · Cited by 569
Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo
Fulga, T. A., Elson-Schwab, I., Khurana, V., Steinhilb, M. L., Spires, T. L., Hyman, B. T., & Feany, M. B. (2007) · Nature Cell Biology · doi:10.1038/ncb1528 · Cited by 452
Clogging of axons by tau, inhibition of axonal traffic and starvation of synapses
Mandelkow�, E. (2003) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.04.007 · Cited by 412
Bassan, M., Zamostiano, R., Davidson, A., Pinhasov, A., Giladi, E., Perl, O., Bassan, H., Blat, C., Gibney, G., Glazner, G. W., et al. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0721283.x · Cited by 394
Self-citationThe Roles of Cyclin-dependent Kinase 5 and Glycogen Synthase Kinase 3 in Tau Hyperphosphorylation
Plattner, F., Angelo, M., & Giese, K. P. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603469200 · Cited by 340
New roles for astrocytes (stars at last)
Ransom, B. R., Behar, T. N., & Nedergaard, M. (2003) · Trends in Neurosciences · doi:10.1016/j.tins.2003.08.006 · Cited by 335
Cloning and Characterization of the Human Activity-dependent Neuroprotective Protein
Zamostiano, R., Pinhasov, A., Gelber, E., Steingart, R. A., Seroussi, E., Giladi, E., Bassan, M., Wollman, Y., Eyre, H. J., Mulley, J. C., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007416200 · Cited by 251
Self-citationActivity-dependent neuroprotective protein: a novel gene essential for brain formation
Pinhasov, A., Mandel, S., Torchinsky, A., Giladi, E., Pittel, Z., Goldsweig, A. M., Servoss, S. J., Brenneman, D. E., & Gozes, I. (2003) · Developmental Brain Research · doi:10.1016/s0165-3806(03)00162-7 · Cited by 239
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–219 of 219
Activity-dependent neuroprotector homeobox protein level in Alzheimer's disease in Taiwanese
Lin, Y., Yang, M., Yang, Y.-H., Chen, W., Lu, C.-Y., Peng, C.-F., Jong, S.-B., Chen, L.-J., Wu, S.-J., Chu, P., et al. (2012) · Genomic Medicine Biomarkers and Health Sciences · doi:10.1016/j.gmbhs.2012.04.004 · Cited by 1
Moleón, V. R., Alende, C., Fotouhi, M., Ayoubi, R., Bolívar, S. G., Laflamme, C., & NeuroSGC/YCharOS/EDDU collaborative group (2024) · F1000Research · doi:10.12688/f1000research.160121.1 · Cited by 1
Saleh, A. Y., Saputra, D. A. Y., Valentina, R., & Susanto, T. D. (2025) · F1000Research · doi:10.12688/f1000research.160416.2 · Cited by 1
Gozes, I., Shapira, G., Lobyntseva, A., & Shomron, N. (2023) · Research Square · doi:10.21203/rs.3.rs-2457393/v1 · Cited by 1
Self-citationHolec, M., & Gozes, I. (2025) · Journal of Molecular Neuroscience · doi:10.1007/s12031-025-02344-5 · Cited by 1
“…2003) and function (Mandel and Gozes 2007; Mandel et al. 2007) and as such, ADNP dysfunction results in cognitive, social, and motor deficits in mouse models (Haco-hen-Kleiman et al. 2018; Karmon et al. 2022; Malishkevich et al. 2015; Shapira et al. 2024; Vulih-Shultzman et al. 2007) and in humans.”
Self-citationS4‐02–04: NAP/SMALL molecule neurotrophics
Gozes, I. (2008) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2008.05.482
Self-citationIs NAP an additional neuroprotector in Alzheimer's disease?
Yang, M., Chen, Y., Lu, C., Tsai, W.-C., Tyan, Y., Liu, Y.-C., Kuo, C., & Hsu, Y.-C. (2013) · Biomarkers and Genomic Medicine · doi:10.1016/j.bgm.2013.07.004
Keservani, R. K., Sharma, A., & Jarouliya, U. (2015)
The Cytoskeleton as a Pharmacological Target in Neurodegenerative Diseases
Oz, S., & Gozes, I. (2012) · Neuromethods · doi:10.1007/978-1-62703-266-7_8
Self-citationBennison, S. A., Blazejewski, S. M., Liu, X., & Toyo‐oka, K. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.26.105015
“Future studies to uncover the mechanism behind the primary phenotype, which we pinpointed as neuritogenesis, will be crucial for therapeutic innovation, including NAP potential homeostatic activity.”
BackgroundMethodInfluentialVityala, Y. (2020) · Indian Journal of Forensic Medicine & Toxicology · doi:10.37506/ijfmt.v14i2.2759
(2008) · Current Opinion in Neurology · doi:10.1097/wco.0b013e32831cbb85
Saleh, A. Y., Saputra, D. A. Y., Valentina, R., & Susanto, T. D. (2025) · F1000Research · doi:10.12688/f1000research.160416.1 · Cited by 1
Novel estrogen replacement combination therapy including the investigational drug davunetidePreprint
Guz, L. S., Galushkin, A., & Gozes, I. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.20.726476
Self-citationLiao, C., Sun, D., & Wang, X. (2026) · Discover Nano · doi:10.1186/s11671-026-04819-9
“For instance, the neuroprotective peptide NAP (daruna-tide), an octapeptide derived from activity-dependent neuroprotective protein (ADNP), has been shown to stabilize microtubules and attenuate tau-related pathology [94].”
Guz, L. S., Galushkin, A., & Gozes, I. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1891428
Self-citationLobyntseva, A., Guz, L. S., Galushkin, A., & Gozes, I. (2026) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2026.101274
Self-citationTargeting protein aggregate co-pathologies in neurodegeneration: a viable therapeutic strategy?
Buck, S. A., Madhavan, S. S., & Sanders, L. H. (2026) · Molecular Neurodegeneration Advances · doi:10.1186/s44477-026-00047-8
Metadata
- Authors
- Vulih-Shultzman, I., Pinhasov, A., Mandel, S., Grigoriadis, N., Touloumi, O., Pittel, Z., & Gozes, I.
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2007-11
- Volume
- 323
- Issue
- 2
- Pages
- 438-449
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2136172091
- Cited by
- 219
- References
- 40
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 12 · 2023: 9 · 2022: 14 · 2021: 9 · 2020: 19 · 2019: 18 · 2018: 7 · 2017: 11 · 2016: 15 · 2015: 13 · 2014: 14 · 2013: 11 · 2012: 13
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- ADNP, NAP peptide, tau hyperphosphorylation, cognitive impairment, learning, neurodegeneration, tauopathy, Alzheimer's disease, mild cognitive impairment, neuroprotection, microtubule binding
- MeSH terms
- Animals, Astrocytes, Cognition Disorders, Female, Learning, Male, Mice, Inbred ICR, Mice, Transgenic, Nerve Tissue Proteins, Oligopeptides, Phosphorylation, tau Proteins, Homeodomain Proteins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
