NNZ-2566, a novel analog of (1–3) IGF-1, as a potential therapeutic agent for fragile X syndrome
Open accessAbstract
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. Previous studies have implicated mGlu5 in the pathogenesis of the disease, and many agents that target the underlying pathophysiology of FXS have focused on mGluR5 modulation. In the present work, a novel pharmacological approach for FXS is investigated. NNZ-2566, a synthetic analog of a naturally occurring neurotrophic peptide derived from insulin-like growth factor-1 (IGF-1), was administered to fmr1 knockout mice correcting learning and memory deficits, abnormal hyperactivity and social interaction, normalizing aberrant dendritic spine density, overactive ERK and Akt signaling, and macroorchidism. Altogether, our results indicate a unique disease-modifying potential for NNZ-2566 in FXS. Most importantly, the present data implicate the IGF-1 molecular pathway in the pathogenesis of FXS. A clinical trial is under way to ascertain whether these findings translate into clinical effects in FXS patients.
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Improvements in dendritic spine abnormalities, astrogliosis, neuroinflammation, glial activation, and downregulation of the MEK-ERK and PI3K-mTOR pathways were seen with trofinetide treatment leading to improvements in behavior and morphology of FXS.
“Improvements in dendritic spine abnormalities, astrogliosis, neuroinflammation, glial activation, and downregulation of the MEK-ERK and PI3K-mTOR pathways were seen with trofinetide treatment leading to improvements in behavior and morphology of FXS [139].”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [139]
The KO mouse was deficient in IGF1 in the brain, and this was normalized with trofinetide treatment for 28 days.
“The KO mouse was deficient in IGF1 in the brain, and this was normalized with trofinetide treatment for 28 days.”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [139]
In fragile X knockout mouse studies, trofinetide had several positive effects at a dose of 100 mg/kg/day.
“In the fragile X knockout (KO), mouse studies trofinetide had several positive effects at a dose of 100 mg/kg/day yielding insight as to why it is beneficial in FXS [139].”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [139]
Cites
The use of a plus-maze to measure anxiety in the mouse
Lister, R. G. (1987) · Psychopharmacology · doi:10.1007/bf00177912 · Cited by 2,617 · see citing works
Assessing nest building in mice
Deacon, R. M. J. (2006) · Nature Protocols · doi:10.1038/nprot.2006.170 · Cited by 1,115 · see citing works
Fmr1 knockout mice: A model to study fragile X mental retardation
THEDUTCHBELGIANFRAGILEXCONSOR (1994) · Cell · doi:10.1016/0092-8674(94)90569-x · Cited by 1,075 · see citing works
Hagerman, R. J., Berry-Kravis, E., Hazlett, H. C., Bailey, D. B., Moine, H., Kooy, R. F., Tassone, F., Gantois, I., Sonenberg, N., Mandel, J. L., et al. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.65 · Cited by 838 · see citing works
Journal of Visualized Experiments
Polanska, U. (2011) · Cited by 824 · see citing works
Rodgers, R. J., & Johnson, N. J. (1995) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(95)00138-m · Cited by 793 · see citing works
Dendritic Spine Structural Anomalies in Fragile-X Mental Retardation Syndrome
Irwin, S. A. (2000) · Cerebral Cortex · doi:10.1093/cercor/10.10.1038 · Cited by 626 · see citing works
Wild-type microglia arrest pathology in a mouse model of Rett syndrome
Derecki, N. C., Cronk, J. C., Lu, Z., Xu, E., Abbott, S. B. G., Guyenet, P. G., & Kipnis, J. (2012) · Nature · doi:10.1038/nature10907 · Cited by 607 · see citing works
Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice
Tropea, D., Giacometti, E., Wilson, N. R., Beard, C., McCurry, C., Fu, D. D., Flannery, R., Jaenisch, R., & Sur, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812394106 · Cited by 593 · see citing works
Regulation of Dendritic Morphogenesis by Ras–PI3K–Akt–mTOR and Ras–MAPK Signaling Pathways
Kumar, V., Zhang, M.-X., Swank, M. W., Kunz, J., & Wu, G.-Y. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2284-05.2005 · Cited by 588 · see citing works
(1994) · PubMed · Cited by 565 · see citing works
Abnormal Development of Dendritic Spines in<i>FMR1</i>Knock-Out Mice
Nimchinsky, E. A., Oberlander, A. M., & Svoboda, K. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-14-05139.2001 · Cited by 560 · see citing works
Dysregulation of mTOR signaling in fragile X syndrome
Sharma, A., Hoeffer, C. A., Takayasu, Y., Miyawaki, T., McBride, S. M., Klann, E., & Zukin, R. S. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3696-09.2010 · Cited by 557 · see citing works
Suppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEP
Yan, Q. J., Rammal, M., Tranfaglia, M., & Bauchwitz, R. P. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.06.004 · Cited by 521 · see citing works
Digging and marble burying in mice: simple methods for in vivo identification of biological impacts
Deacon, R. M. J. (2006) · Nature Protocols · doi:10.1038/nprot.2006.20 · Cited by 508 · see citing works
Chronic Pharmacological mGlu5 Inhibition Corrects Fragile X in Adult Mice
Michalon, A., Sidorov, M., Ballard, T. M., Ozmen, L., Spooren, W., Wettstein, J. G., Jaeschke, G., Bear, M. F., & Lindemann, L. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.009 · Cited by 489 · see citing works
Garber, K. B., Visootsak, J., & Warren, S. T. (2008) · European Journal of Human Genetics · doi:10.1038/ejhg.2008.61 · Cited by 477 · see citing works
Rett Syndrome Microglia Damage Dendrites and Synapses by the Elevated Release of Glutamate
Maezawa, I., & Jin, L. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.5966-09.2010 · Cited by 348 · see citing works
EphB/syndecan-2 signaling in dendritic spine morphogenesis
Ethell, I. M., Irie, F., Kalo, M. S., Couchman, J. R., Pasquale, E. B., & Yamaguchi, Y. (2001) · Neuron · doi:10.1016/s0896-6273(01)00440-8 · Cited by 309 · see citing works
Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus
Henkemeyer, M. J., Itkis, O. S., Ngo, M., Hickmott, P. W., & Ethell, I. M. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200306033 · Cited by 302 · see citing works
Henderson, C., Wijetunge, L., Kinoshita, M. N., Shumway, M., Hammond, R. S., Postma, F. R., Brynczka, C., Rush, R., Thomas, A., Paylor, R., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004218 · Cited by 249 · see citing works
Ethell, I. M., & Yamaguchi, Y. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.144.3.575 · Cited by 209 · see citing works
Expanding the Mind: Insulin-Like Growth Factor I and Brain Development
D’Ercole, A. J., & Ye, P. (2008) · Endocrinology · doi:10.1210/en.2008-0920 · Cited by 208 · see citing works
Altered mTOR signaling and enhanced CYFIP2 expression levels in subjects with fragile X syndrome
Hoeffer, C. A., Sanchez, E., Hagerman, R. J., Mu, Y., Nguyen, D. V., Wong, H., Whelan, A. M., Zukin, R. S., Klann, E., & Tassone, F. (2012) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2012.00768.x · Cited by 198 · see citing works
Hippocampal lesions, species-typical behaviours and anxiety in mice
Deacon, R. M. J., & Rawlins, J. N. P. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.05.027 · Cited by 193 · see citing works
Astrocytes prevent abnormal neuronal development in the fragile X mouse.
Jacobs, S., & Doering, L. C. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5027-09.2010 · Cited by 170 · see citing works
A fragile balance: FMR1 expression levels
Oostra, B. A., & Willemsen, R. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg298 · Cited by 128 · see citing works
AFQ056, a new mGluR5 antagonist for treatment of fragile X syndrome
Levenga, J., Hayashi, S., de Vrij, F. M. S., Koekkoek, S. K. E., van der Linde, H. C., Nieuwenhuizen, I. M., Song, C., Buijsen, R. A. M., Pop, A. S., Gomez‐Mancilla, B., et al. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.01.022 · Cited by 122 · see citing works
Sara, V. R., Carlsson‐Skwirut, C., Bergman, T., Jörnvall, H., Roberts, P., Crawford, M., Håkansson, L., Civalero, I., & Nordberg, A. K. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(89)80032-4 · Cited by 112 · see citing works
Wei, H. H., Lu, X. M., Shear, D. A., Waghray, A., Yao, C., Tortella, F. C., & Dave, J. R. (2009) · Journal of Neuroinflammation · doi:10.1186/1742-2094-6-19 · Cited by 80 · see citing works
NNZ-2566: A Gly–Pro–Glu analogue with neuroprotective efficacy in a rat model of acute focal stroke
Bickerdike, M. J., Thomas, G. B., Batchelor, D. C., Sirimanne, E. S., Leong, W., Lin, H., Sieg, F., Wen, J., Brimble, M. A., Harris, P. W. R., et al. (2009) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2008.12.003 · Cited by 68 · see citing works
Verrilli, M. A. L., Pirola, C. J., Pascual, M. M., Dominici, F. P., Turyn, D., & Gironacci, M. M. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.05912.x · Cited by 65 · see citing works
Baker, A., Batchelor, D. C., Thomas, G. B., Wen, J., Rafiee, M., Lin, H., & Guan, J. (2005) · Neuropeptides · doi:10.1016/j.npep.2004.11.001 · Cited by 62 · see citing works
Guan, J., & Gluckman, P. D. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00256.x · Cited by 60 · see citing works
Corvin, A. P., Molinos, I., Little, G., Donohoe, G., Gill, M., Morris, D. W., & Tropea, D. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.05.029 · Cited by 57 · see citing works
Behavioral phenotyping of mice lacking the KATP channel subunit Kir6.2
Deacon, R. M. J., Brook, R. C., Meyer, D. H., Haeckel, O., Ashcroft, F. M., Miki, T., Seino, S., & Liss, B. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.01.013 · Cited by 51 · see citing works
The Successive Alleys Test of Anxiety in Mice and Rats
Deacon, R. M. J. (2013) · Journal of Visualized Experiments · doi:10.3791/2705 · Cited by 49 · see citing works
Svedin, P., Guan, J., Mathai, S., Zhang, R., Wang, X., Gustavsson, M., Hagberg, H., & Mallard, C. E. (2007) · Developmental Neuroscience · doi:10.1159/000105480 · Cited by 35 · see citing works
Fragile X syndrome. Molecular and clinical insights and treatment issues.
Hagerman, R. J. (1997) · Europe PMC (PubMed Central) · Cited by 34 · see citing works
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Hagerman, R. J., Berry-Kravis, E., Hazlett, H. C., Bailey, D. B., Moine, H., Kooy, R. F., Tassone, F., Gantois, I., Sonenberg, N., Mandel, J. L., et al. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.65 · Cited by 838 · see citing works
An Update on Psychopharmacological Treatment of Autism Spectrum Disorder
Aishworiya, R., Valica, T., Hagerman, R., & Restrepo, B. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01183-1 · Cited by 233 · see citing works
Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders
Delhaye, S., & Bardoni, B. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00997-9 · Cited by 155 · see citing works
Fragile X targeted pharmacotherapy: lessons learned and future directions
Erickson, C. A., Davenport, M. H., Schaefer, T. L., Wink, L. K., Pedapati, E. V., Sweeney, J. A., Fitzpatrick, S. E., Brown, W. T., Budimirovic, D. B., Hagerman, R. J., et al. (2017) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-017-9186-9 · Cited by 153 · see citing works
Treating Rett syndrome: from mouse models to human therapies
Vashi, N., & Justice, M. J. (2019) · Mammalian Genome · doi:10.1007/s00335-019-09793-5 · Cited by 111 · see citing works
Berry-Kravis, E., Horrigan, J. P., Tartaglia, N., Hagerman, R., Kolevzon, A., Erickson, C. A., Hatti, S., Snape, M., Yaroshinsky, A., Stoms, G., et al. (2020) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2020.04.019 · Cited by 102 · see citing works
Self-citationThe Therapeutic Potential of Insulin-Like Growth Factor-1 in Central Nervous System Disorders
Costales, J. L., & Kolevzon, A. (2016) · Neuroscience and Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.01.001 · Cited by 93 · see citing works
Caldwell, A. L. M., Sancho, L., Deng, J., Bosworth, A., Miglietta, A., Diedrich, J. K., Shokhirev, M. N., & Allen, N. J. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01150-1 · Cited by 86 · see citing works
Vahdatpour, C., Dyer, A. H., & Tropea, D. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00450 · Cited by 76 · see citing works
Targets for Drug Therapy for Autism Spectrum Disorder: Challenges and Future Directions
Lacivita, E., Perrone, R., Margari, L., & Leopoldo, M. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00965 · Cited by 66 · see citing works
Díaz‐Caneja, C. M., State, M. W., Hagerman, R. J., Jacquemont, S., Marín, Ó., Bagni, C., Umbricht, D., Simonoff, E. A., Andres-Trelles, F., Kaale, A., et al. (2021) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2021.02.020 · Cited by 54 · see citing works
Neurobiologically-based treatments in Rett syndrome: opportunities and challenges
Kaufmann, W. E., Stallworth, J. L., Everman, D. B., & Skinner, S. A. (2016) · Expert Opinion on Orphan Drugs · doi:10.1080/21678707.2016.1229181 · Cited by 50 · see citing works
Treatment of autistic spectrum disorder with insulin-like growth factors
Riikonen, R. (2016) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2016.08.005 · Cited by 50 · see citing works
Gaboxadol Normalizes Behavioral Abnormalities in a Mouse Model of Fragile X Syndrome
Cogram, P., Deacon, R. M. J., Warner‐Schmidt, J. L., von Schimmelmann, M. J., Abrahams, B. S., & During, M. J. (2019) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2019.00141 · Cited by 48 · see citing works
Ge, L., Liu, S., Rubin, L., Lazarovici, P., & Zheng, W. (2022) · Cells · doi:10.3390/cells11040666 · Cited by 47 · see citing works
Keam, S. J. (2023) · Drugs · doi:10.1007/s40265-023-01883-8 · Cited by 46 · see citing works
Réthelyi, J., Vincze, K., Schall, D., Glennon, J. C., & Berkel, S. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105330 · Cited by 49 · see citing works
The Search for an Effective Therapy to Treat Fragile X Syndrome: Dream or Reality?
Castagnola, S., Bardoni, B., & Maurin, T. (2017) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2017.00015 · Cited by 40 · see citing works
Schaefer, T. L., Davenport, M. H., Grainger, L. M., Robinson, C. K., Earnheart, A. T., Stegman, M., Lang, A. L., Ashworth, A. A., Molinaro, G., Huber, K. M., et al. (2017) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-017-9184-y · Cited by 37 · see citing works
Review of targeted treatments in fragile X syndrome
Ligsay, A., & Hagerman, R. J. (2016) · Intractable & Rare Diseases Research · doi:10.5582/irdr.2016.01045 · Cited by 37 · see citing works
Hudu, S. A., El-Migdadi, F., Al-Qtaitat, A., Almehmadi, M. M., Alsaiari, A. A., Allahyani, M. A., Aljuaid, A., Salih, M. M., Alghamdi, A., Alrofaidi, M. A., et al. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12155114 · Cited by 32 · see citing works
Linker, S. B., Mendes, A. P. D., & Marchetto, M. C. (2020) · Molecular Autism · doi:10.1186/s13229-020-00359-w · Cited by 31 · see citing works
Pharmacotherapy for Fragile X Syndrome: Progress to Date
Davenport, M. H., Schaefer, T. L., Friedmann, K., Fitzpatrick, S. E., & Erickson, C. A. (2016) · Drugs · doi:10.1007/s40265-016-0542-y · Cited by 31 · see citing works
Natural AD-Like Neuropathology in Octodon degus: Impaired Burrowing and Neuroinflammation
Deacon, R. M. J., Altimiras, F. J., Bazán-León, E. A., Pyarasani, R. D., Nachtigall, F. M., Santos, L. S., Tsolaki, A. G., Pednekar, L., Kishore, U., Biekofsky, R. R., et al. (2015) · Current Alzheimer Research · doi:10.2174/1567205012666150324181652 · Cited by 28 · see citing works
Criss‐crossing autism spectrum disorder and adult neurogenesis
Bicker, F., Nardi, L., Maier, J., Vasić, V., & Schmeißer, M. J. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15501 · Cited by 26 · see citing works
Neurotrophic Factors in Mouse Models of Autism Spectrum Disorder: Focus on BDNF and IGF-1
Reim, D., & Schmeißer, M. J. (2017) · Advances in anatomy, embryology and cell biology · doi:10.1007/978-3-319-52498-6_7 · Cited by 27 · see citing works
Preclinical testing of the ketogenic diet in fragile X mice
Westmark, P. R., Gutierrez, A., Gholston, A. K., Wilmer, T. M., & Westmark, C. J. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104687 · Cited by 25 · see citing works
Reyes, S. T., Deacon, R. M. J., Guo, S. G., Altimiras, F. J., Castillo, J. B., van der Wildt, B., Morales, A. P., Park, J. H., Klamer, D., Rosenberg, J., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-94079-7 · Cited by 22 · see citing works
Rett Syndrome and Fragile X Syndrome: Different Etiology With Common Molecular Dysfunctions
Bach, S., Shovlin, S., Moriarty, M. J., Bardoni, B., & Tropea, D. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.764761 · Cited by 23 · see citing works
Fragile X syndrome clinical trials: exploring parental decision‐making
D'Amanda, C. S., Peay, H. L., Wheeler, A., Turbitt, E., & Biesecker, B. B. (2019) · Journal of Intellectual Disability Research · doi:10.1111/jir.12605 · Cited by 21 · see citing works
IGF-1 as a Potential Therapy for Spinocerebellar Ataxia Type 3
Lin, Y.-S., Cheng, W., Chang, J., Lin, T., Chao, Y., & Liu, C. (2022) · Biomedicines · doi:10.3390/biomedicines10020505 · Cited by 19 · see citing works
Bausch, A. E., Ehinger, R., Straubinger, J., Zerfass, P., Nann, Y., & Łukowski, R. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.05.040 · Cited by 18 · see citing works
Cioana, M., Michalski, B., & Fahnestock, M. L. (2020) · Autism Research · doi:10.1002/aur.2291 · Cited by 16 · see citing works
Chen, D., Li, H., Zhao, Q., Song, J., Chen, L., & Yu, J. (2021) · Psychiatry Research · doi:10.1016/j.psychres.2021.113717 · Cited by 17 · see citing works
Changes in insulin‐like growth factor signaling alter phenotypes in Fragile X Mice
Wise, T. L. (2016) · Genes Brain & Behavior · doi:10.1111/gbb.12340 · Cited by 16 · see citing works
Pharmacological Rescue of Hippocampal Fear Learning Deficits in Fragile X Syndrome
Martinez, L. A., & Tejada-Simon, M. V. (2018) · Molecular Neurobiology · doi:10.1007/s12035-017-0819-5 · Cited by 14 · see citing works
Martinez, L. A., & Tejada-Simon, M. V. (2018) · Molecular Neurobiology · doi:10.1007/s12035-017-0666-4 · Cited by 13 · see citing works
An Update on Psychopharmacological Treatment of Autism Spectrum Disorder
Aishworiya, R., Valica, T., Hagerman, R. J., & Restrepo, B. (2024) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.24022006 · Cited by 15 · see citing works
Camillo, L., Pozzi, M., Bernardo, P., Pisano, S., & Nobile, M. (2024) · Drug Design Development and Therapy · doi:10.2147/dddt.s383133 · Cited by 12 · see citing works
Fragile X Syndrome: Lessons Learned and What New Treatment Avenues Are on the Horizon
Hagerman, R. J., & Hagerman, P. J. (2021) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-052120-090147 · Cited by 12 · see citing works
Shen, J., Liu, L., Yang, Y., Zhou, M., Xu, S., Zhang, W., & Zhang, C. (2024) · Cureus · doi:10.7759/cureus.65393 · Cited by 10 · see citing works
Consumption of Breast Milk Is Associated with Decreased Prevalence of Autism in Fragile X Syndrome
Westmark, C. J. (2021) · Nutrients · doi:10.3390/nu13061785 · Cited by 10 · see citing works
Initial analysis of peripheral lymphocytic extracellular signal related kinase activation in autism
Erickson, C. A., Ray, B., Wink, L. K., Bayon, B. L., Pedapati, E. V., Shaffer, R. C., Schaefer, T. L., & Lahiri, D. K. (2016) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.09.003 · Cited by 10 · see citing works
Fragile X Syndrome and Targeted Treatments
Tassanakijpanich, N., Cabal-Herrera, A. M., Salcedo‐Arellano, M. J., & Hagerman, R. J. (2020) · Journal of Biomedicine and Translational Research · doi:10.14710/jbtr.v6i1.7321 · Cited by 10 · see citing works
Cryptic Host Defense Peptides: Multifaceted Activity and Prospects for Medicinal Chemistry
Costa, B. O., & Franco, O. L. (2020) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026620666200325112425 · Cited by 7 · see citing works
Lymphocytic Extracellular Signal–Regulated Kinase Dysregulation in Autism Spectrum Disorder
Erickson, C. A., Tessier, C. R., Groß, C., Pedapati, E. V., Wink, L. K., Dominick, K. C., Shaffer, R. C., Rosselot, H., Hong, M. P., Bantel, A. P., et al. (2023) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2022.09.437 · Cited by 6 · see citing works
Retracted: Nrf2: a novel therapeutic target in fragile X syndrome is modulated by NNZ2566
Deacon, R. M. J., Hurley, M. J., Rebolledo, C., Snape, M., Altimiras, F. J., Farías, L., Pino, M., Biekofsky, R. R., Glass, L., & Cogram, P. (2017) · Genes Brain & Behavior · doi:10.1111/gbb.12373 · Cited by 6 · see citing works
RetractedThe novel potent GSK3 inhibitor AF3581 reverts fragile X syndrome phenotype
Porceddu, P. F., Ciampoli, M., Romeo, E., Garrone, B., Durando, L., Milanese, C., Giorgio, F. P. D., & Reggiani, A. M. (2021) · Human Molecular Genetics · doi:10.1093/hmg/ddab251 · Cited by 6 · see citing works
The effect of modulation Piezo2 by IGF-1 on tactile hypersensitivity in BTBR model mice
Zhai, J., Hao, H., Xu, Z., Tomoda, A., Zhang, X., Wang, X., Liu, Y., Cao, X., Li, D., Zhang, Y., et al. (2025) · Life Sciences · doi:10.1016/j.lfs.2025.123449 · Cited by 5 · see citing works
Watkins, L. V., Moon, S., Burrows, L., Tromans, S. J., Barwell, J., & Shankar, R. (2024) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2024.2323605 · Cited by 5 · see citing works
The role of oligopeptides in preventing autism
Steinman, G., & Mankuta, D. (2020) · Medical Hypotheses · doi:10.1016/j.mehy.2020.109604 · Cited by 5 · see citing works
Review of Salient Investigational Drugs for the Treatment of Fragile X Syndrome
Munshi, K. R., Pawlowski, K. G., Gonzalez–Heydrich, J., & Picker, J. D. (2017) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2016.0200 · Cited by 5 · see citing works
Structural models of viral insulin‐like peptides and their analogs
Gorai, B., & Vashisth, H. (2022) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.26410 · Cited by 5 · see citing works
Arora, T., Caviedes, P. A., & Sharma, S. K. (2019) · Neurotoxicity Research · doi:10.1007/s12640-019-00130-x · Cited by 5 · see citing works
Altable, M. (2021) · doi:10.32388/ko4c77 · Cited by 3 · see citing works
Trofinetide Improves Cognitive Function in APP/PS1 Mice by Suppressing Inflammation and Apoptosis
Chen, M., Ning, Y., Yang, H., & Jia, J. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05500-5 · Cited by 4 · see citing works
Overview of Targeted Double-Blind, Placebo-Controlled Clinical Trials in Fragile X Syndrome
Ligsay, A., Hagerman, R. J., & Berry‐Kravis, E. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804461-2.00019-6 · Cited by 4 · see citing works
Altable, M., & de la Serna, J. M. (2021) · doi:10.32388/ko4c77.2 · Cited by 3 · see citing works
Subramanian, M. P., Mills, W. T., Paranjpe, M. D., Onuchukwu, U. S., Inamdar, M., Maytin, A. R., Li, X., Pomerantz, J. L., & Meffert, M. K. (2023) · iScience · doi:10.1016/j.isci.2023.108676 · Cited by 3 · see citing works
Stanfield, A. C., & McKechanie, A. G. (2025) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2025.2510408 · Cited by 3 · see citing works
Emerging Role of Epigenetics in Human Neurodevelopmental Disorders
Mastrototaro, G., & Sessa, A. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-812215-0.00009-1 · Cited by 3 · see citing works
Emerging role of epigenetics in human neurodevelopmental disorders
Mastrototaro, G., Sessa, A., & Zaghi, M. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-18661-5.00022-1 · Cited by 3 · see citing works
The Emerging Role of Phosphodiesterase Inhibitors in Fragile X Syndrome and Autism Spectrum Disorder
Thomas, S. D., Mohammed, H. A., Hamad, M. I. K., Öz, M., Statsenko, Y. A., & Sadek, B. S. (2025) · Pharmaceuticals · doi:10.3390/ph18101507 · Cited by 2 · see citing works
Reflections on Clinical Trials in Fragile X Syndrome
Jønch, A. E., & Jacquemont, S. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804461-2.00020-2 · Cited by 2 · see citing works
Genetic and Pharmacological Reversibility of Phenotypes in Mouse Models of Autism Spectrum Disorder
Schroeder, J. C., Deliu, E., Novarino, G., & Schmeißer, M. J. (2017) · Advances in anatomy, embryology and cell biology · doi:10.1007/978-3-319-52498-6_10 · Cited by 2 · see citing works
Verma, J., Singh, R. K., Paul, S., Gupta, S., Gupta, A. K., Sharma, A. K., Kumar, M., Mehan, S., Samant, R., & Tongra, M. (2026) · Metabolic Brain Disease · doi:10.1007/s11011-026-01866-0 · Cited by 1 · see citing works
Gogliotti, R. G., & Conn, P. J. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.259 · Cited by 1 · see citing works
Wannes, S., Ahmer, I. E., Rjiba, K., Jemmali, N., Abdallah, H. H., Haj, R. B., Achour, A., Bouzidi, H., Saad, A., Mougou-Zerelli, S., et al. (2023) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2023.101550 · Cited by 1 · see citing works
Snape, M. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.12306-6
Transcriptomic and epigenetic changes after the phenotypic rescue of a Rett Syndrome mouse model
Vargas-Landín, D. B. (2021) · UWA Profiles and Research Repository (UWA) · doi:10.26182/9kh2-8h70
Levy, T., Holder, J. L., Horrigan, J. P., Snape, M. F., McMorn, A., Layton, C., Silver, H., Friedman, K., Grosman, H. E., Underwood, S. J., et al. (2024) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2024.100393
Molecular Interactions of Viral Insulin/ IGF ‐Like Peptides With Zebrafish Receptors
Levintov, L., & Vashisth, H. (2026) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.70168
Depoortère, R., Tranfaglia, M. R., & Newman‐Tancredi, A. (2026) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2026.111681
Dissecting the role of calcium signaling in Fragile X syndrome
Castagnola, S. (2019) · theses.fr (ABES) · doi:10.70675/3d35096bz79d0z46edz8a70zb783a8f60257
Pathophysiological consequences of a Fragile X missense mutation
Garcia, M. P. (2020) · theses.fr (ABES) · doi:10.70675/b8e86263z5926z4a83zbaf6z0f61bf2d15f9
Yue, S., Young, C., Garg, A., Sarovich, T., Chen, L., Dickerson, K., & Wang, Z.-J. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1858227
Carver, A. J., Williamson, E. G., & Stevens, H. E. (2026) · Cells · doi:10.3390/cells15191759
BindingDB (2019) · UC San Diego · doi:10.7270/q2377c5d
- Authors
- Deacon, R. M. J., Glass, L., Snape, M., Hurley, M. J., Altimiras, F. J., Biekofsky, R. R., & Cogram, P.
- Affiliations
- Imperial College London (GB)
- University of Chile (CL)
- Fraunhofer Chile Research Foundation (CL)
- Corresponding author
- Glass, Larry
- Cogram, Patricia
- Venue
- NeuroMolecular Medicine
- Published
- 2015-01-23
- Volume
- 17
- Issue
- 1
- Pages
- 71-82
- ISSN
- 1535-1084 (ISSN-L)
- 1559-1174
- OpenAlex
- W2044280569
- Cited by
- 78
- References
- 39
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 5 · 2021: 13 · 2020: 8 · 2019: 5 · 2018: 2 · 2017: 13 · 2016: 9 · 2015: 2
- FWCI
- 5.92
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (tdm)
- Locations
- NeuroMolecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
- Universidad de Chile (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Keywords
- fragile X syndrome, IGF-1 signaling, FMRP, mGluR5, Fmr1 knockout mice, learning and memory impairment, hyperactivity, social interaction, dendritic spine density, ERK signaling, Akt signaling, macroorchidism, disease-modifying therapy, intellectual disability
- MeSH terms
- Animals, Anxiety, Brain, Conditioning, Classical, Dendrites, Drug Evaluation, Preclinical, Exploratory Behavior, Fear, Fragile X Syndrome, Glutamates, Insulin-Like Growth Factor I, Interpersonal Relations, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Nesting Behavior, Oligopeptides, Testis, Mice, Knockout, Neuroprotective Agents, Maze Learning, MAP Kinase Signaling System, Proto-Oncogene Proteins c-akt, Mice, Fragile X Messenger Ribonucleoprotein 1
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