Literature Review: The Role of NRXN-3 and Neurexin-3 Proteins in the Mechanisms of Schizophrenia

Aoto, J., Martinelli, D. C., Malenka, R. C., Tabuchi, K., & Südhof, T. C. (2013). Presynaptic Neurexin-3 Alternative Splicing Trans-Synaptically Controls Postsynaptic AMPA-Receptor Trafficking. Cell, 154(1), 75–88. https://doi.org/10.1016/j.cell.2013.05.060

Bebbington, P. E., Angermeyer, M., Azorin, J.-M., Brugha, T., Kilian, R., Johnson, S., Toumi, M., Kornfeld, Å., & EuroSC Research Group. (2005). The European Schizophrenia Cohort. Social Psychiatry and Psychiatric Epidemiology, 40(9), 707–717. https://doi.org/10.1007/s00127-005-0955-5

Ben-Shachar, D., & Laifenfeld, D. (2004). Mitochondria, Synaptic Plasticity, And Schizophrenia. In International Review of Neurobiology (Vol. 59, pp. 273–296). Academic Press. https://doi.org/10.1016/S0074-7742(04)59011-6

Boxer, E. E., Seng, C., Lukacsovich, D., Kim, J., Schwartz, S., Kennedy, M. J., Földy, C., & Aoto, J. (2021). Neurexin-3 defines synapse- and sex-dependent diversity of GABAergic inhibition in ventral subiculum. Cell Reports, 37(10), 110098. https://doi.org/10.1016/j.celrep.2021.110098

Brisch, R., Saniotis, A., Wolf, R., Bielau, H., Bernstein, H.-G., Steiner, J., Bogerts, B., Braun, K., Jankowski, Z., Kumaratilake, J., Henneberg, M., & Gos, T. (2014). The Role of Dopamine in Schizophrenia from a Neurobiological and Evolutionary Perspective: Old Fashioned, but Still in Vogue. Frontiers in Psychiatry, 5, 47. https://doi.org/10.3389/fpsyt.2014.00047

Caire, M. J., Reddy, V., & Varacallo, M. (2023). Physiology, Synapse. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK526047/

Canitano, R., & Pallagrosi, M. (2017). Autism Spectrum Disorders and Schizophrenia Spectrum Disorders: Excitation/Inhibition Imbalance and Developmental Trajectories. Frontiers in Psychiatry, 8. https://www.frontiersin.org/articles/10.3389/fpsyt.2017.00069

Correll, C. U., & Schooler, N. R. (2020). Negative Symptoms in Schizophrenia: A Review and Clinical Guide for Recognition, Assessment, and Treatment. Neuropsychiatric Disease and Treatment, 16, 519–534. https://doi.org/10.2147/NDT.S225643

Crabtree, G. W., & Gogos, J. A. (2014). Synaptic plasticity, neural circuits, and the emerging role of altered short-term information processing in schizophrenia. Frontiers in Synaptic Neuroscience, 6. https://www.frontiersin.org/articles/10.3389/fnsyn.2014.00028

Cromwell, H. C., Mears, R. P., Wan, L., & Boutros, N. N. (2008). Sensory Gating: A Translational Effort From Basic to Clinical Science. Clinical EEG and Neuroscience, 39(2), 69–72. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4127047/

Dai, J., Aoto, J., & Südhof, T. C. (2019). Alternative Splicing of Presynaptic Neurexins Differentially Controls Postsynaptic NMDA and AMPA Receptor Responses. Neuron, 102(5), 993-1008.e5. https://doi.org/10.1016/j.neuron.2019.03.032

Das, T. K., Kumar, J., Francis, S., Liddle, P. F., & Palaniyappan, L. (2020). Parietal lobe and disorganisation syndrome in schizophrenia and psychotic bipolar disorder: A bimodal connectivity study. Psychiatry Research: Neuroimaging, 303, 111139. https://doi.org/10.1016/j.pscychresns.2020.111139

Drummond, J. B., Tucholski, J., Haroutunian, V., & Meador-Woodruff, J. H. (2013). Transmembrane AMPA receptor regulatory protein (TARP) dysregulation in anterior cingulate cortex in schizophrenia. Schizophrenia Research, 147(1), 32–38. https://doi.org/10.1016/j.schres.2013.03.010

Feichtinger, R. G., Preisel, M., Brugger, K., Wortmann, S. B., & Mayr, J. A. (2023). Case Report—An Inherited Loss-of-Function NRXN3 Variant Potentially Causes a Neurodevelopmental Disorder with Autism Consistent with Previously Described 14q24.3-31.1 Deletions. Genes, 14(6), 1217. https://doi.org/10.3390/genes14061217

Fleischhacker, W. W., Arango, C., Arteel, P., Barnes, T. R. E., Carpenter, W., Duckworth, K., Galderisi, S., Halpern, L., Knapp, M., Marder, S. R., Moller, M., Sartorius, N., & Woodruff, P. (2014). Schizophrenia—Time to Commit to Policy Change. Schizophrenia Bulletin, 40(Suppl 3), S165. https://doi.org/10.1093/schbul/sbu006

Goff, D. C., & Coyle, J. T. (2001). The Emerging Role of Glutamate in the Pathophysiology and Treatment of Schizophrenia. American Journal of Psychiatry, 158(9), 1367–1377. https://doi.org/10.1176/appi.ajp.158.9.1367

Hishimoto, A., Liu, Q.-R., Drgon, T., Pletnikova, O., Walther, D., Zhu, X.-G., Troncoso, J. C., & Uhl, G. R. (2007). Neurexin 3 polymorphisms are associated with alcohol dependence and altered expression of specific isoforms. Human Molecular Genetics, 16(23), 2880–2891. https://doi.org/10.1093/hmg/ddm247

Hu, X., Zhang, J., Jin, C., Mi, W., Wang, F., Ma, W., Ma, C., Yang, Y., Li, W., Zhang, H., Du, B., Li, K., Liu, C., Wang, L., Lu, T., Zhang, H., Lv, L., Zhang, D., & Yue, W. (2013). Association study of NRXN3 polymorphisms with schizophrenia and risperidone-induced bodyweight gain in Chinese Han population. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 43, 197–202. https://doi.org/10.1016/j.pnpbp.2012.12.007

ICD-10 Version:2016. (n.d.). Retrieved July 19, 2023, from https://icd.who.int/browse10/2016/en#/F20-F29

Ishizuka, K., Yoshida, T., Kawabata, T., Imai, A., Mori, H., Kimura, H., Inada, T., Okahisa, Y., Egawa, J., Usami, M., Kushima, I., Morikawa, M., Okada, T., Ikeda, M., Branko, A., Mori, D., Someya, T., Iwata, N., & Ozaki, N. (2020). Functional characterization of rare NRXN1 variants identified in autism spectrum disorders and schizophrenia. Journal of Neurodevelopmental Disorders, 12(1), 25. https://doi.org/10.1186/s11689-020-09325-2

Jahangir, M., Zhou, J.-S., Lang, B., & Wang, X.-P. (2021). GABAergic System Dysfunction and Challenges in Schizophrenia Research. Frontiers in Cell and Developmental Biology, 9, 663854. https://doi.org/10.3389/fcell.2021.663854

Kapur, S., Agid, O., Mizrahi, R., & Li, M. (2006). How antipsychotics work—From receptors to reality. NeuroRx, 3(1), 10–21. https://doi.org/10.1016/j.nurx.2005.12.003

Karlsgodt, K. H., Sun, D., & Cannon, T. D. (2010). Structural and Functional Brain Abnormalities in Schizophrenia. Current Directions in Psychological Science, 19(4), 226–231. https://doi.org/10.1177/0963721410377601

Luo, C., Liu, J., Wang, X., Mao, X., Zhou, H., & Liu, Z. (2019). Pharmacogenetic Correlates of Antipsychotic-Induced Weight Gain in the Chinese Population. Neuroscience Bulletin, 35(3), 561–580. https://doi.org/10.1007/s12264-018-0323-6

Luo, F., Sclip, A., Merrill, S., & Südhof, T. C. (2021). Neurexins regulate presynaptic GABAB-receptors at central synapses. Nature Communications, 12(1), Article 1. https://doi.org/10.1038/s41467-021-22753-5

Megan Maroney, P. (2020). An Update on Current Treatment Strategies and Emerging Agents for the Management of Schizophrenia. 26. https://www.ajmc.com/view/an-update-on-current-treatment-strategies-and-emerging-agents-for-the-management-of-schizophrenia

Missler, M., Zhang, W., Rohlmann, A., Kattenstroth, G., Hammer, R. E., Gottmann, K., & Südhof, T. C. (2003). α-Neurexins couple Ca2+ channels to synaptic vesicle exocytosis. Nature, 423(6943), Article 6943. https://doi.org/10.1038/nature01755

Nicita, F., Di Giacomo, M., Palumbo, O., Ferri, E., Maiorani, D., Vigevano, F., Carella, M., & Capuano, A. (2015). Neurological features of 14q24-q32 interstitial deletion: Report of a new case. Molecular Cytogenetics, 8, 93. https://doi.org/10.1186/s13039-015-0196-6

PubChem. (n.d.). NRXN3—Neurexin 3 (human). Retrieved August 6, 2023, from https://pubchem.ncbi.nlm.nih.gov/gene/NRXN3/human

Reissner, C., Runkel, F., & Missler, M. (2013). Neurexins. Genome Biology, 14(9), 213. https://doi.org/10.1186/gb-2013-14-9-213

Snyder, M. A., & Gao, W.-J. (2020). NMDA receptor hypofunction for schizophrenia revisited: Perspectives from epigenetic mechanisms. Schizophrenia Research, 217, 60–70. https://doi.org/10.1016/j.schres.2019.03.010

Sons, M. S., Busche, N., Strenzke, N., Moser, T., Ernsberger, U., Mooren, F. C., Zhang, W., Ahmad, M., Steffens, H., Schomburg, E. D., Plomp, J. J., & Missler, M. (2006). α-Neurexins are required for efficient transmitter release and synaptic homeostasis at the mouse neuromuscular junction. Neuroscience, 138(2), 433–446. https://doi.org/10.1016/j.neuroscience.2005.11.040

Stampanoni Bassi, M., Iezzi, E., Gilio, L., Centonze, D., & Buttari, F. (2019). Synaptic Plasticity Shapes Brain Connectivity: Implications for Network Topology. International Journal of Molecular Sciences, 20(24), 6193. https://doi.org/10.3390/ijms20246193

Stephan, K. E., Friston, K. J., & Frith, C. D. (2009). Dysconnection in Schizophrenia: From Abnormal Synaptic Plasticity to Failures of Self-monitoring. Schizophrenia Bulletin, 35(3), 509–527. https://doi.org/10.1093/schbul/sbn176

Stępnicki, P., Kondej, M., & Kaczor, A. A. (2018). Current Concepts and Treatments of Schizophrenia. Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry, 23(8), 2087. https://doi.org/10.3390/molecules23082087

Südhof, T. C. (2008). Neuroligins and Neurexins Link Synaptic Function to Cognitive Disease. Nature, 455(7215), 903–911. https://doi.org/10.1038/nature07456

Südhof, T. C. (2017). Synaptic Neurexin Complexes: A Molecular Code for the Logic of Neural Circuits. Cell, 171(4), 745–769. https://doi.org/10.1016/j.cell.2017.10.024

Wang, X., Christian, K. M., Song, H., & Ming, G. (2018). Synaptic dysfunction in complex psychiatric disorders: From genetics to mechanisms. Genome Medicine, 10, 9. https://doi.org/10.1186/s13073-018-0518-5

Yuan, H., Wang, Q., Liu, Y., Yang, W., He, Y., Gusella, J. F., Song, J., & Shen, Y. (2018). A rare exonic NRXN3 deletion segregating with neurodevelopmental and neuropsychiatric conditions in a three-generation Chinese family. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : The Official Publication of the International Society of Psychiatric Genetics, 177(6), 589–595. https://doi.org/10.1002/ajmg.b.32673

Zhang, K., Liao, P., Wen, J., & Hu, Z. (2022). Synaptic plasticity in schizophrenia pathophysiology. IBRO Neuroscience Reports, 13, 478–487. https://doi.org/10.1016/j.ibneur.2022.10.008

Zhang, R., Jiang, H., Liu, Y., & He, G. (2023). Structure, function, and pathology of Neurexin-3. Genes & Diseases, 10(5), 1908–1919. https://doi.org/10.1016/j.gendis.2022.04.008

Zhou, M., Derakhshanian, S., Rath, A., Bertrand, S., DeGraw, C., Barlow, R., Menard, A., Kaye, A. M., Hasoon, J., Cornett, E. M., Kaye, A. D., Viswanath, O., & Urits, I. (2020). Asenapine Transdermal Patch for the Management of Schizophrenia. Psychopharmacology Bulletin, 50(4), 60–82. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511145/