Login Register Cart 0
Generic placeholder image

CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

Unraveling the Role of Neuroligin3 in Autism Spectrum Disorders: Pathophysiological Insights and Targeted Therapies

Author(s): Fatima Azzahrae EL Yacoubi, Mohamed Oukabli, Azeddine Ibrahimi, Hassan Kisra and Mounia Bensaid*

Volume 23, Issue 7, 2024

Published on: 31 July, 2023

Page: [801 - 811] Pages: 11

DOI: 10.2174/1871527323666230727102244

Price: $65

Abstract

Autism Spectrum Disorder is a neurodevelopmental disorder characterized by impaired social and communication skills, repetitive behaviors, and/or restricted interests with a prevalence of as high as 1% of children. Autism spectrum has strongly associated with genetic factors and exhibits wide clinical and heterogeneous genetic architecture. Most genes associated with Autism are involved in neuronal and synaptic development. The neuroligin3, the sex-linked gene on the X chromosome, was the first gene to be associated with a monogenic form of Autism. Neuroligin3 is a postsynaptic cell adhesion protein involved in synapse transmission, brain formation, and neuronal development. In this review, we provide recent findings on different mutations in the Neuroligin3 gene linked to Autism spectrum disorder and their molecular pathway effect. We also give the behavioral, and synaptic alterations reported in the Neuroligin3 animal model of Autism and the potential therapeutic strategies targeting the biological processes and the main symptoms of autism spectrum disorder. In addition, we discuss the use of novel technologies like induced pluripotent stem cells from Autistic patients that have the potential to differentiate in human neurons and therefore have a variety of applications in therapy and biomedical studies to search specific biomarkers, and develop systems for screening chemical molecules in human cells to discover target therapies.

Next »
Graphical Abstract

[1]
Lord C, Elsabbagh M, Baird G, Veenstra-Vanderweele J. Autism spectrum disorder. Lancet 2018; 392(10146): 508-20.
[http://dx.doi.org/10.1016/S0140-6736(18)31129-2] [PMID: 30078460]
[2]
Geschwind DH. Advances in autism. Annu Rev Med 2009; 60(1): 367-80.
[http://dx.doi.org/10.1146/annurev.med.60.053107.121225] [PMID: 19630577]
[3]
Lyall K, Croen L, Daniels J, et al. The changing epidemiology of autism spectrum disorders. Annu Rev Public Health 2017; 38(1): 81-102.
[http://dx.doi.org/10.1146/annurev-publhealth-031816-044318] [PMID: 28068486]
[4]
Fombonne E. The prevalence of autism. JAMA 2003; 289(1): 87-9.
[http://dx.doi.org/10.1001/jama.289.1.87] [PMID: 12503982]
[5]
Santangelo SL, Tsatsanis K. What is known about autism: Genes, brain, and behavior. Am J Pharmacogenomics 2005; 5(2): 71-92.
[http://dx.doi.org/10.2165/00129785-200505020-00001] [PMID: 15813671]
[6]
Folstein SE, Rosen-Sheidley B. Genetics of austim: Complex aetiology for a heterogeneous disorder. Nat Rev Genet 2001; 2(12): 943-55.
[http://dx.doi.org/10.1038/35103559] [PMID: 11733747]
[7]
Folstein SE, Santangelo SL, Gilman SE, et al. Predictors of cognitive test patterns in autism families. J Child Psychol Psychiatry 1999; 40(7): 1117-28.
[http://dx.doi.org/10.1111/1469-7610.00528] [PMID: 10576540]
[8]
O’Roak BJ, Vives L, Girirajan S, et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 2012; 485(7397): 246-50.
[http://dx.doi.org/10.1038/nature10989] [PMID: 22495309]
[9]
De Rubeis S, He X, Goldberg AP, et al. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature 2014; 515(7526): 209-15.
[http://dx.doi.org/10.1038/nature13772] [PMID: 25363760]
[10]
Pinto D, Delaby E, Merico D, et al. Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am J Hum Genet 2014; 94(5): 677-94.
[http://dx.doi.org/10.1016/j.ajhg.2014.03.018] [PMID: 24768552]
[11]
Bolliger MF, Frei K, Winterhalter KH, Gloor SM. Identification of a novel neuroligin in humans which binds to PSD-95 and has a widespread expression. Biochem J 2001; 356(2): 581-8.
[http://dx.doi.org/10.1042/bj3560581] [PMID: 11368788]
[12]
Bolliger MF, Pei J, Maxeiner S, Boucard AA, Grishin NV, Südhof TC. Unusually rapid evolution of Neuroligin-4 in mice. Proc Natl Acad Sci USA 2008; 105(17): 6421-6.
[http://dx.doi.org/10.1073/pnas.0801383105] [PMID: 18434543]
[13]
Jamain S, Quach H, Betancur C, et al. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 2003; 34(1): 27-9.
[http://dx.doi.org/10.1038/ng1136] [PMID: 12669065]
[14]
Yoshida T, Yamagata A, Imai A, et al. Canonical versus non-canonical transsynaptic signaling of neuroligin 3 tunes development of sociality in mice. Nat Commun 2021; 12(1): 1848.
[http://dx.doi.org/10.1038/s41467-021-22059-6] [PMID: 33758193]
[15]
Ichtchenko K, Nguyen T, Südhof TC. Structures, alternative splicing, and neurexin binding of multiple neuroligins. J Biol Chem 1996; 271(5): 2676-82.
[http://dx.doi.org/10.1074/jbc.271.5.2676] [PMID: 8576240]
[16]
Philibert RA, Winfield SL, Sandhu HK, Martin BM, Ginns EI. The structure and expression of the human neuroligin-3 gene. Gene 2000; 246(1-2): 303-10.
[http://dx.doi.org/10.1016/S0378-1119(00)00049-4] [PMID: 10767552]
[17]
Südhof TC. Neuroligins and neurexins link synaptic function to cognitive disease. Nature 2008; 455(7215): 903-11.
[http://dx.doi.org/10.1038/nature07456] [PMID: 18923512]
[18]
Varoqueaux F, Aramuni G, Rawson RL, et al. Neuroligins determine synapse maturation and function. Neuron 2006; 51(6): 741-54.
[http://dx.doi.org/10.1016/j.neuron.2006.09.003] [PMID: 16982420]
[19]
Uchigashima M, Cheung A, Futai K. Neuroligin-3: A circuit-specific synapse organizer that shapes normal function and autism spectrum disorder-associated dysfunction. Front Mol Neurosci 2021; 14: 749164.
[http://dx.doi.org/10.3389/fnmol.2021.749164] [PMID: 34690695]
[20]
Irie M, Hata Y, Takeuchi M, et al. Binding of Neuroligins to PSD-95. Science 1997; 277(5331): 1511-5.
[http://dx.doi.org/10.1126/science.277.5331.1511] [PMID: 9278515]
[21]
Nguyen TA, Lehr AW, Roche KW. Neuroligins and neurodevelopmental disorders: X-linked genetics. Front Synaptic Neurosci 2020; 12: 33.
[http://dx.doi.org/10.3389/fnsyn.2020.00033] [PMID: 32848696]
[22]
Budreck EC, Scheiffele P. Neuroligin-3 is a neuronal adhesion protein at GABAergic and glutamatergic synapses. Eur J Neurosci 2007; 26(7): 1738-48.
[http://dx.doi.org/10.1111/j.1460-9568.2007.05842.x] [PMID: 17897391]
[23]
Song JY, Ichtchenko K, Südhof TC, Brose N. Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses. Proc Natl Acad Sci 1999; 96(3): 1100-5.
[http://dx.doi.org/10.1073/pnas.96.3.1100] [PMID: 9927700]
[24]
Etherton M, Földy C, Sharma M, et al. Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function. Proc Natl Acad Sci 2011; 108(33): 13764-9.
[http://dx.doi.org/10.1073/pnas.1111093108] [PMID: 21808020]
[25]
Vieira MM, Jeong J, Roche KW. The role of NMDA receptor and neuroligin rare variants in synaptic dysfunction underlying neurodevelopmental disorders. Curr Opin Neurobiol 2021; 69: 93-104.
[http://dx.doi.org/10.1016/j.conb.2021.03.001] [PMID: 33823469]
[26]
Graf ER, Zhang X, Jin SX, Linhoff MW, Craig AM. Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins. Cell 2004; 119(7): 1013-26.
[http://dx.doi.org/10.1016/j.cell.2004.11.035] [PMID: 15620359]
[27]
Stogsdill JA, Ramirez J, Liu D, et al. Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis. Nature 2017; 551(7679): 192-7.
[http://dx.doi.org/10.1038/nature24638] [PMID: 29120426]
[28]
Chih B, Afridi SK, Clark L, Scheiffele P. Disorder-associated mutations lead to functional inactivation of neuroligins. Hum Mol Genet 2004; 13(14): 1471-7.
[http://dx.doi.org/10.1093/hmg/ddh158] [PMID: 15150161]
[29]
Liu JJ, Grace KP, Horner RL, Cortez MA, Shao Y, Jia Z. Neuroligin 3 R451C mutation alters electroencephalography spectral activity in an animal model of autism spectrum disorders. Mol Brain 2017; 10(1): 10.
[http://dx.doi.org/10.1186/s13041-017-0290-2] [PMID: 28385162]
[30]
Xu X, Xiong Z, Zhang L, et al. Variations analysis of NLGN3 and NLGN4X gene in Chinese autism patients. Mol Biol Rep 2014; 41(6): 4133-40.
[http://dx.doi.org/10.1007/s11033-014-3284-5] [PMID: 24570023]
[31]
Trobiani L, Meringolo M, Diamanti T, et al. The neuroligins and the synaptic pathway in autism spectrum disorder. Neurosci Biobehav Rev 2020; 119: 37-51.
[http://dx.doi.org/10.1016/j.neubiorev.2020.09.017] [PMID: 32991906]
[32]
Quartier A, Courraud J, Thi Ha T, et al. Novel mutations in NLGN3 causing autism spectrum disorder and cognitive impairment. Hum Mutat 2019; 40(11): 2021-32.
[http://dx.doi.org/10.1002/humu.23836] [PMID: 31184401]
[33]
C Yuen RK, Merico D, Bookman M, et al. Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. Nat Neurosci 2017; 20(4): 602-11.
[http://dx.doi.org/10.1038/nn.4524] [PMID: 28263302]
[34]
Talebizadeh Z, Bittel DC, Veatch OJ, et al. Do known mutations in neuroligin genes (NLGN3 and NLGN4) cause autism? J Autism Dev Disord 2004; 34(6): 735-6.
[http://dx.doi.org/10.1007/s10803-004-5295-x] [PMID: 15679194]
[35]
Volaki K, Pampanos A, Kitsiou-Tzeli S, et al. Mutation screening in the Greek population and evaluation of NLGN3 and NLGN4X genes causal factors for autism. Psychiatr Genet 2013; 23(5): 198-203.
[http://dx.doi.org/10.1097/YPG.0b013e3283643644] [PMID: 23851596]
[36]
Steinberg KM, Ramachandran D, Patel VC, Shetty AC, Cutler DJ, Zwick ME. Identification of rare X-linked neuroligin variants by massively parallel sequencing in males with autism spectrum disorder. Mol Autism 2012; 3(1): 8.
[http://dx.doi.org/10.1186/2040-2392-3-8] [PMID: 23020841]
[37]
Landini M, Merelli I, Raggi M, et al. Association analysis of noncoding variants in neuroligins 3 and 4X genes with autism spectrum disorder in an Italian cohort. Int J Mol Sci 2016; 17(10): 1765.
[http://dx.doi.org/10.3390/ijms17101765] [PMID: 27782075]
[38]
Blasi F, Bacchelli E, Pesaresi G, Carone S, Bailey AJ, Maestrini E. Absence of coding mutations in the X-linked genes neuroligin 3 and neuroligin 4 in individuals with autism from the IMGSAC collection. Am J Med Genet B Neuropsychiatr Genet 2006; 141B(3): 220-1.
[http://dx.doi.org/10.1002/ajmg.b.30287] [PMID: 16508939]
[39]
Etherton MR, Tabuchi K, Sharma M, Ko J, Südhof TC. An autism-associated point mutation in the neuroligin cytoplasmic tail selectively impairs AMPA receptor-mediated synaptic transmission in hippocampus. EMBO J 2011; 30(14): 2908-19.
[http://dx.doi.org/10.1038/emboj.2011.182] [PMID: 21642956]
[40]
Radyushkin K, Hammerschmidt K, Boretius S, et al. Neuroligin-3-deficient mice: Model of a monogenic heritable form of autism with an olfactory deficit. Genes Brain Behav 2009; 8(4): 416-25.
[http://dx.doi.org/10.1111/j.1601-183X.2009.00487.x] [PMID: 19243448]
[41]
Rothwell PE, Fuccillo MV, Maxeiner S, et al. Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors. Cell 2014; 158(1): 198-212.
[http://dx.doi.org/10.1016/j.cell.2014.04.045] [PMID: 24995986]
[42]
Modi B, Pimpinella D, Pazienti A, Zacchi P, Cherubini E, Griguoli M. Possible Implication of the CA2 hippocampal circuit in social cognition deficits observed in the Neuroligin 3 Knock-Out Mouse, a non-syndromic animal model of autism. Front Psychiatry 2019; 10: 513.
[http://dx.doi.org/10.3389/fpsyt.2019.00513] [PMID: 31379628]
[43]
Baudouin SJ, Gaudias J, Gerharz S, et al. Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism. Science 2012; 338(6103): 128-32.
[http://dx.doi.org/10.1126/science.1224159] [PMID: 22983708]
[44]
Tabuchi K, Blundell J, Etherton MR, et al. A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science 2007; 318(5847): 71-6.
[http://dx.doi.org/10.1126/science.1146221] [PMID: 17823315]
[45]
Shipman SL, Nicoll RA. A subtype-specific function for the extracellular domain of neuroligin 1 in hippocampal LTP. Neuron 2012; 76(2): 309-16.
[http://dx.doi.org/10.1016/j.neuron.2012.07.024] [PMID: 23083734]
[46]
Pizzarelli R, Cherubini E. Developmental regulation of GABAergic signalling in the hippocampus of neuroligin 3 R451C knock-in mice: An animal model of Autism. Front Cell Neurosci 2013; 7: 85.
[http://dx.doi.org/10.3389/fncel.2013.00085] [PMID: 23761734]
[47]
Földy C, Malenka RC, Südhof TC. Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling. Neuron 2013; 78(3): 498-509.
[http://dx.doi.org/10.1016/j.neuron.2013.02.036] [PMID: 23583622]
[48]
Zhang B, Chen LY, Liu X, Maxeiner S, Lee SJ, Gokce O. Neuroligins sculpt cerebellar purkinje-cell circuits by differential control of distinct classes of synapses. neuron 2015; 87(4): 781-96.
[49]
Pensado-López A, Veiga-Rúa S, Carracedo Á, Allegue C, Sánchez L. Experimental models to study autism spectrum disorders: HiPSCs, rodents and zebrafish. Genes 2020; 11(11): 1376.
[http://dx.doi.org/10.3390/genes11111376] [PMID: 33233737]
[50]
Laumonnier F, Bonnet-Brilhault F, Gomot M, et al. X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am J Hum Genet 2004; 74(3): 552-7.
[http://dx.doi.org/10.1086/382137] [PMID: 14963808]
[51]
Yan J, Oliveira G, Coutinho A, et al. Analysis of the neuroligin 3 and 4 genes in autism and other neuropsychiatric patients. Mol Psychiatry 2005; 10(4): 329-32.
[http://dx.doi.org/10.1038/sj.mp.4001629] [PMID: 15622415]
[52]
Lovaas OI. Behavioral treatment and normal educational and intellectual functioning in young autistic children. J Consult Clin Psychol 1987; 55(1): 3-9.
[http://dx.doi.org/10.1037/0022-006X.55.1.3] [PMID: 3571656]
[53]
Mesibov GB, Shea V. The TEACCH program in the era of evidence-based practice. J Autism Dev Disord 2010; 40(5): 570-9.
[http://dx.doi.org/10.1007/s10803-009-0901-6] [PMID: 19937103]
[54]
Mesibov GB. Formal and informal measures on the effectiveness of the TEACCH programme. Autism 1997; 1(1): 25-35.
[http://dx.doi.org/10.1177/1362361397011005]
[55]
Virues-Ortega J, Julio FM, Pastor-Barriuso R. The TEACCH program for children and adults with autism: A meta-analysis of intervention studies. Clin Psychol Rev 2013; 33(8): 940-53.
[http://dx.doi.org/10.1016/j.cpr.2013.07.005] [PMID: 23988454]
[56]
Panerai S, Zingale M, Trubia G, et al. Special education versus inclusive education: The role of the TEACCH program. J Autism Dev Disord 2009; 39(6): 874-82.
[http://dx.doi.org/10.1007/s10803-009-0696-5] [PMID: 19205860]
[57]
Whalen C, Schreibman L. Joint attention training for children with autism using behavior modification procedures. J Child Psychol Psychiatry 2003; 44(3): 456-68.
[http://dx.doi.org/10.1111/1469-7610.00135] [PMID: 12635974]
[58]
Frost L. The picture exchange communication system. Perspect Lang Learn Educ 2002; 9(2): 13-6.
[http://dx.doi.org/10.1044/lle9.2.13]
[59]
Cidav Z, Munson J, Estes A, Dawson G, Rogers S, Mandell D. Cost offset associated with early start denver model for children with autism. J Am Acad Child Adolesc Psychiatry 2017; 56(9): 777-83.
[http://dx.doi.org/10.1016/j.jaac.2017.06.007] [PMID: 28838582]
[60]
Fuller EA, Oliver K, Vejnoska SF, Rogers SJ. The effects of the early start denver model for children with autism spectrum disorder: A meta-analysis. Brain Sci 2020; 10(6): 368.
[http://dx.doi.org/10.3390/brainsci10060368] [PMID: 32545615]
[61]
McDougle CJ, Holmes JP, Carlson DC, Pelton GH, Cohen DJ, Price LH. A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders. Arch Gen Psychiatry 1998; 55(7): 633-41.
[http://dx.doi.org/10.1001/archpsyc.55.7.633] [PMID: 9672054]
[62]
Germann D, Kurylo N, Han F. Risperidone. profiles drug subst excip relat methodol 2012; 37: 313-61.
[63]
Al-Huseini S, Al-Barhoumi A, Al-Balushi M, et al. Effectiveness and adverse effects of risperidone in children with autism spectrum disorder in a naturalistic clinical setting at a university hospital in oman. Autism Res Treat 2022; 2022: 1-7.
[http://dx.doi.org/10.1155/2022/2313851] [PMID: 35127178]
[64]
Hollander E, Soorya L, Chaplin W, et al. A double-blind placebo-controlled trial of fluoxetine for repetitive behaviors and global severity in adult autism spectrum disorders. Am J Psychiatry 2012; 169(3): 292-9.
[http://dx.doi.org/10.1176/appi.ajp.2011.10050764] [PMID: 22193531]
[65]
Melke J, Goubran Botros H, Chaste P, et al. Abnormal melatonin synthesis in autism spectrum disorders. Mol Psychiatry 2008; 13(1): 90-8.
[http://dx.doi.org/10.1038/sj.mp.4002016] [PMID: 17505466]
[66]
Cortesi F, Giannotti F, Sebastiani T, Panunzi S, Valente D. Controlled-release melatonin, singly and combined with cognitive behavioural therapy, for persistent insomnia in children with autism spectrum disorders: A randomized placebo-controlled trial. J Sleep Res 2012; 21(6): 700-9.
[http://dx.doi.org/10.1111/j.1365-2869.2012.01021.x] [PMID: 22616853]
[67]
Wasdell MB, Jan JE, Bomben MM, et al. A randomized, placebo-controlled trial of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities. J Pineal Res 2008; 44(1): 57-64.
[PMID: 18078449]
[68]
Wright B, Sims D, Smart S, et al. Melatonin versus placebo in children with autism spectrum conditions and severe sleep problems not amenable to behaviour management strategies: A randomised controlled crossover trial. J Autism Dev Disord 2011; 41(2): 175-84.
[http://dx.doi.org/10.1007/s10803-010-1036-5] [PMID: 20535539]
[69]
Hörnberg H, Pérez-Garci E, Schreiner D, et al. Rescue of oxytocin response and social behaviour in a mouse model of autism. Nature 2020; 584(7820): 252-6.
[http://dx.doi.org/10.1038/s41586-020-2563-7] [PMID: 32760004]
[70]
Andari E, Duhamel JR, Zalla T, Herbrecht E, Leboyer M, Sirigu A. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci 2010; 107(9): 4389-94.
[http://dx.doi.org/10.1073/pnas.0910249107] [PMID: 20160081]
[71]
Burrows EL, Laskaris L, Koyama L, et al. A neuroligin-3 mutation implicated in autism causes abnormal aggression and increases repetitive behavior in mice. Mol Autism 2015; 6(1): 62.
[http://dx.doi.org/10.1186/s13229-015-0055-7] [PMID: 26583067]
[72]
Cao P, Xing J, Cao Y, et al. Clinical effects of repetitive transcranial magnetic stimulation combined with atomoxetine in the treatment of attention: Deficit hyperactivity disorder. Neuropsychiatr Dis Treat 2018; 14: 3231-40.
[http://dx.doi.org/10.2147/NDT.S182527] [PMID: 30538481]
[73]
Hellings JA, Arnold LE, Han JC. Dopamine antagonists for treatment resistance in autism spectrum disorders: review and focus on BDNF stimulators loxapine and amitriptyline. Expert Opin Pharmacother 2017; 18(6): 581-8.
[http://dx.doi.org/10.1080/14656566.2017.1308483] [PMID: 28335658]
[74]
Doers ME, Musser MT, Nichol R, et al. iPSC-derived forebrain neurons from FXS individuals show defects in initial neurite outgrowth. Stem Cells Dev 2014; 23(15): 1777-87.
[http://dx.doi.org/10.1089/scd.2014.0030] [PMID: 24654675]
[75]
Marchetto MCN, Carromeu C, Acab A, et al. A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 2010; 143(4): 527-39.
[http://dx.doi.org/10.1016/j.cell.2010.10.016] [PMID: 21074045]
[76]
Kenny EM, Cormican P, Furlong S, et al. Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders. Mol Psychiatry 2014; 19(8): 872-9.
[http://dx.doi.org/10.1038/mp.2013.127] [PMID: 24126926]
[77]
Iossifov I, O’Roak BJ, Sanders SJ, et al. The contribution of de novo coding mutations to autism spectrum disorder. Nature 2014; 515(7526): 216-21.
[http://dx.doi.org/10.1038/nature13908] [PMID: 25363768]
[78]
Redin C, Gérard B, Lauer J, et al. Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing. J Med Genet 2014; 51(11): 724-36.
[http://dx.doi.org/10.1136/jmedgenet-2014-102554] [PMID: 25167861]
[79]
Yanagi K, Kaname T, Wakui K, Hashimoto O, Fukushima Y, Naritomi K. Identification of four novel synonymous substitutions in the x-linked genes neuroligin 3 and neuroligin 4X in japanese patients with autistic spectrum disorder. Autism Res Treat 2012; 2012: 1-5.
[http://dx.doi.org/10.1155/2012/724072] [PMID: 22934180]
[80]
Mikhailov A, Fennell A, Plong-on O, et al. Screening of NLGN3 and NLGN4X genes in Thai children with autism spectrum disorder. Psychiatr Genet 2014; 24(1): 42-3.
[http://dx.doi.org/10.1097/YPG.0000000000000019] [PMID: 24362370]
[81]
Hegde R, Hegde S, Kulkarni SS, Pandurangi A, Gai PB, Das KK. Genetic analysis of the postsynaptic transmembrane X-linked neuroligin 3 gene in autism. Genomics Inform 2021; 19(4): e44.
[http://dx.doi.org/10.5808/gi.21029] [PMID: 35012288]
[82]
Yu J, He X, Yao D, Li Z, Li H, Zhao Z. A sex-specific association of common variants of neuroligin genes (NLGN3 and NLGN4X) with autism spectrum disorders in a Chinese Han cohort. Behav Brain Funct 2011; 7(1): 13.
[http://dx.doi.org/10.1186/1744-9081-7-13] [PMID: 21569590]
[83]
Hosie S, Malone DT, Liu S, et al. Altered amygdala excitation and CB1 Receptor modulation of aggressive behavior in the neuroligin-3(R451C) mouse model of autism. Front Cell Neurosci 2018; 12: 234.
[http://dx.doi.org/10.3389/fncel.2018.00234] [PMID: 30123111]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy