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
Review Article

Gene Therapy for Neuropsychiatric Disorders: Potential Targets and Tools

Author(s): Seyed H. Shahcheraghi, Jamshid Ayatollahi, Marzieh Lotfi*, Alaa A.A. Aljabali, Mazhar S. Al-Zoubi, Pritam K. Panda, Vijay Mishra, Saurabh Satija, Nitin B. Charbe, Ángel Serrano-Aroca, Bojlul Bahar, Kazuo Takayama, Rohit Goyal, Amit Bhatia, Abdulmajeed G. Almutary, Abdullah M. Alnuqaydan, Yachana Mishra, Poonam Negi, Aaron Courtney, Paul A. McCarron, Hamid A. Bakshi and Murtaza M. Tambuwala*

Volume 22, Issue 1, 2023

Published on: 11 April, 2022

Page: [51 - 65] Pages: 15

DOI: 10.2174/1871527321666220304153719

open access plus

Abstract

Neuropsychiatric disorders that affect the central nervous system cause considerable pressures on the health care system and have a substantial economic burden on modern societies. The present treatments based on available drugs are mostly ineffective and often costly. The molecular process of neuropsychiatric disorders is closely connected to modifying the genetic structures inherited or caused by damage, toxic chemicals, and some current diseases. Gene therapy is presently an experimental concept for neurological disorders. Clinical applications endeavor to alleviate the symptoms, reduce disease progression, and repair defective genes. Implementing gene therapy in inherited and acquired neurological illnesses entails the integration of several scientific disciplines, including virology, neurology, neurosurgery, molecular genetics, and immunology. Genetic manipulation has the power to minimize or cure illness by inducing genetic alterations at endogenous loci. Gene therapy that involves treating the disease by deleting, silencing, or editing defective genes and delivering genetic material to produce therapeutic molecules has excellent potential as a novel approach for treating neuropsychiatric disorders. With the recent advances in gene selection and vector design quality in targeted treatments, gene therapy could be an effective approach. This review article will investigate and report the newest and the most critical molecules and factors in neuropsychiatric disorder gene therapy. Different genome editing techniques available will be evaluated, and the review will highlight preclinical research of genome editing for neuropsychiatric disorders while also evaluating current limitations and potential strategies to overcome genome editing advancements.

Keywords: Neuropsychiatric disorders, gene therapy, genes, autism, bipolar disorder, molecular targets, therapeutics, bloodbrain barrier.

« Previous Next »
Graphical Abstract

[1]
Bloem BR, Henderson EJ, Dorsey ER, et al. Integrated and patient-centred management of Parkinson’s disease: A network model for reshaping chronic neurological care. Lancet Neurol 2020; 19(7): 623-34.
[http://dx.doi.org/10.1016/S1474-4422(20)30064-8] [PMID: 32464101]
[2]
Alural B, Genc S, Haggarty SJ. Diagnostic and therapeutic potential of microRNAs in neuropsychiatric disorders: Past, present, and future. Prog Neuropsychopharmacol Biol Psychiatry 2017; 73: 87-103.
[http://dx.doi.org/10.1016/j.pnpbp.2016.03.010] [PMID: 27072377]
[3]
Miyoshi K, Morimura Y. Clinical manifestations of neuropsychiatric disorders. In: Miyoshi K, Morimura Y, Maeda K, Eds. Neuropsychiatric Disorders. Tokyo: Springer 2010.
[http://dx.doi.org/10.1007/978-4-431-53871-4_1]
[4]
Bakulski KM, Halladay A, Hu VW, Mill J, Fallin MD. Epigenetic research in neuropsychiatric disorders: The “tissue issue”. Curr Behav Neurosci Rep 2016; 3(3): 264-74.
[http://dx.doi.org/10.1007/s40473-016-0083-4] [PMID: 28093577]
[5]
Novellino F, Saccà V, Donato A, et al. Innate immunity: A common denominator between neurodegenerative and neuropsychiatric diseases. Int J Mol Sci 2020; 21(3): 1115.
[http://dx.doi.org/10.3390/ijms21031115] [PMID: 32046139]
[6]
Gyertyán I. How can preclinical cognitive research further neuropsychiatric drug discovery? Chances and challenges. Expert Opin Drug Discov 2020; 15(6): 659-70.
[http://dx.doi.org/10.1080/17460441.2020.1739645] [PMID: 32183541]
[7]
Zhu X, Need AC, Petrovski S, Goldstein DB. One gene, many neuropsychiatric disorders: Lessons from mendelian diseases. Nat Neurosci 2014; 17(6): 773-81.
[http://dx.doi.org/10.1038/nn.3713] [PMID: 24866043]
[8]
Pilla RV, Kozielska M, Johnson M, et al. Structural models describing placebo treatment effects in schizophrenia and other neuropsychiatric disorders. Clin Pharmacokinet 2011; 50(7): 429-50.
[http://dx.doi.org/10.2165/11590590-000000000-00000] [PMID: 21651312]
[9]
Rehman S, Nabi B, Pottoo FH, Baboota S, Ali J. Nanoparticle based gene therapy approach: A pioneering rebellion in the management of psychiatric disorders. Curr Gene Ther 2020; 20(3): 164-73.
[http://dx.doi.org/10.2174/1566523220666200607185903] [PMID: 32515310]
[10]
Ryskalin L, Limanaqi F, Frati A, Busceti CL, Fornai F. mTOR-related brain dysfunctions in neuropsychiatric disorders. Int J Mol Sci 2018; 19(8): 2226.
[http://dx.doi.org/10.3390/ijms19082226] [PMID: 30061532]
[11]
Boutouja F, Stiehm CM, Platta HW. mTOR: A cellular regulator interface in health and disease. Cells 2019; 8(1): 18.
[http://dx.doi.org/10.3390/cells8010018] [PMID: 30609721]
[12]
O’Connell EM, Lohoff FW. Proprotein convertase subtilisin/Kexin Type 9 (PCSK9) in the brain and relevance for neuropsychiatric disorders. Front Neurosci 2020; 14: 609.
[http://dx.doi.org/10.3389/fnins.2020.00609] [PMID: 32595449]
[13]
Sun X. Target genes of transcription factor Sp4 in neuronal development. In: Sackler School of Graduate Biomedical Sciences Tufts University. 2013.
[14]
Gargus JJ. Ion channel functional candidate genes in multigenic neuropsychiatric disease. Biol Psychiatry 2006; 60(2): 177-85.
[http://dx.doi.org/10.1016/j.biopsych.2005.12.008] [PMID: 16497276]
[15]
Sakurai T. The role of cell adhesion molecules in brain wiring and neuropsychiatric disorders. Mol Cell Neurosci 2017; 81: 4-11.
[http://dx.doi.org/10.1016/j.mcn.2016.08.005] [PMID: 27561442]
[16]
Beroun A, Mitra S, Michaluk P, Pijet B, Stefaniuk M, Kaczmarek L. MMPs in learning and memory and neuropsychiatric disorders. Cell Mol Life Sci 2019; 76(16): 3207-28.
[http://dx.doi.org/10.1007/s00018-019-03180-8] [PMID: 31172215]
[17]
Kuehner JN, Bruggeman EC, Wen Z, Yao B. Epigenetic regulations in neuropsychiatric disorders. Front Genet 2019; 10: 268.
[http://dx.doi.org/10.3389/fgene.2019.00268] [PMID: 31019524]
[18]
Snyder SH, Ferris CD. Novel neurotransmitters and their neuropsychiatric relevance. Am J Psychiatry 2000; 157(11): 1738-51.
[http://dx.doi.org/10.1176/appi.ajp.157.11.1738] [PMID: 11058466]
[19]
Pei L, Wallace DC. Mitochondrial etiology of neuropsychiatric disorders. Biol Psychiatry 2018; 83(9): 722-30.
[http://dx.doi.org/10.1016/j.biopsych.2017.11.018] [PMID: 29290371]
[20]
Olney JW. Excitotoxicity, apoptosis and neuropsychiatric disorders. Curr Opin Pharmacol 2003; 3(1): 101-9.
[http://dx.doi.org/10.1016/S1471489202000024] [PMID: 12550750]
[21]
Morris G, Stubbs B, Köhler CA, et al. The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis. Sleep Med Rev 2018; 41: 255-65.
[http://dx.doi.org/10.1016/j.smrv.2018.03.007] [PMID: 29759891]
[22]
Bauer ME, Teixeira AL. Inflammation in psychiatric disorders: What comes first? Ann N Y Acad Sci 2019; 1437(1): 57-67.
[http://dx.doi.org/10.1111/nyas.13712] [PMID: 29752710]
[23]
Xu B, Hsu P-K, Karayiorgou M, Gogos JA. MicroRNA dysregulation in neuropsychiatric disorders and cognitive dysfunction. Neurobiol Dis 2012; 46(2): 291-301.
[http://dx.doi.org/10.1016/j.nbd.2012.02.016] [PMID: 22406400]
[24]
Lett TA, Chakravarty MM, Felsky D, et al. The genome-wide supported microRNA-137 variant predicts phenotypic heterogeneity within schizophrenia. Mol Psychiatry 2013; 18(4): 443-50.
[http://dx.doi.org/10.1038/mp.2013.17] [PMID: 23459466]
[25]
Wang Y, Hu Z, Ju P, et al. Viral vectors as a novel tool for clinical and neuropsychiatric research applications. Gen Psychiatr 2018; 31(2): e000015.
[http://dx.doi.org/10.1136/gpsych-2018-000015] [PMID: 30582128]
[26]
Hocquemiller M, Giersch L, Audrain M, Parker S, Cartier N. Adeno-associated virus-based gene therapy for CNS diseases. Hum Gene Ther 2016; 27(7): 478-96.
[http://dx.doi.org/10.1089/hum.2016.087] [PMID: 27267688]
[27]
Gurda BL, De Guilhem De Lataillade A, Bell P, et al. Evaluation of AAV-mediated gene therapy for central nervous system disease in canine mucopolysaccharidosis VII. Mol Ther 2016; 24(2): 206-16.
[http://dx.doi.org/10.1038/mt.2015.189] [PMID: 26447927]
[28]
Lykken EA, Shyng C, Edwards RJ, Rozenberg A, Gray SJ. Recent progress and considerations for AAV gene therapies targeting the central nervous system. J Neurodev Disord 2018; 10(1): 16.
[http://dx.doi.org/10.1186/s11689-018-9234-0] [PMID: 29776328]
[29]
Ramamoorth M, Narvekar A. Non viral vectors in gene therapy- an overview. J Clin Diagn Res 2015; 9(1): GE01-6.
[http://dx.doi.org/10.7860/JCDR/2015/10443.5394] [PMID: 25738007]
[30]
Pérez-Martínez FC, Guerra J, Posadas I, Ceña V. Barriers to non-viral vector-mediated gene delivery in the nervous system. Pharm Res 2011; 28(8): 1843-58.
[http://dx.doi.org/10.1007/s11095-010-0364-7] [PMID: 21225319]
[31]
Sapolsky RM. Gene therapy for psychiatric disorders. Am J Psychiatry 2003; 160(2): 208-20.
[http://dx.doi.org/10.1176/appi.ajp.160.2.208] [PMID: 12562564]
[32]
Benger M, Kinali M, Mazarakis ND. Autism spectrum disorder: Prospects for treatment using gene therapy. Mol Autism 2018; 9(1): 39.
[http://dx.doi.org/10.1186/s13229-018-0222-8] [PMID: 29951185]
[33]
Frith U, Happé F. Autism spectrum disorder. Curr Biol 2005; 15(19): R786-90.
[http://dx.doi.org/10.1016/j.cub.2005.09.033] [PMID: 16213805]
[34]
Campisi L, Imran N, Nazeer A, Skokauskas N, Azeem MW. Autism spectrum disorder. Br Med Bull 2018; 127(1): 91-100.
[http://dx.doi.org/10.1093/bmb/ldy026] [PMID: 30215678]
[35]
Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 1999; 23(2): 185-8.
[http://dx.doi.org/10.1038/13810] [PMID: 10508514]
[36]
Kishino T, Lalande M, Wagstaff J. UBE3A/E6-AP mutations cause Angelman syndrome. Nat Genet 1997; 15(1): 70-3.
[http://dx.doi.org/10.1038/ng0197-70] [PMID: 8988171]
[37]
Splawski I, Timothy KW, Sharpe LM, et al. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 2004; 119(1): 19-31.
[http://dx.doi.org/10.1016/j.cell.2004.09.011] [PMID: 15454078]
[38]
van Slegtenhorst M, de Hoogt R, Hermans C, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science 1997; 277(5327): 805-8.
[http://dx.doi.org/10.1126/science.277.5327.805] [PMID: 9242607]
[39]
Verkerk AJ, Pieretti M, Sutcliffe JS, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991; 65(5): 905-14.
[http://dx.doi.org/10.1016/0092-8674(91)90397-H] [PMID: 1710175]
[40]
Hopkins AL, Groom CR. The druggable genome. Nat Rev Drug Discov 2002; 1(9): 727-30.
[http://dx.doi.org/10.1038/nrd892] [PMID: 12209152]
[41]
Bourgeron T. From the genetic architecture to synaptic plasticity in autism spectrum disorder. Nat Rev Neurosci 2015; 16(9): 551-63.
[http://dx.doi.org/10.1038/nrn3992] [PMID: 26289574]
[42]
Sato A. mTOR, a potential target to treat autism spectrum disorder. CNS Neurol Disord Drug Targets 2016; 15(5): 533-43.
[http://dx.doi.org/10.2174/1871527315666160413120638] [PMID: 27071790]
[43]
Sato A, Kasai S, Kobayashi T, et al. Rapamycin reverses impaired social interaction in mouse models of tuberous sclerosis complex. Nat Commun 2012; 3(1): 1292.
[http://dx.doi.org/10.1038/ncomms2295] [PMID: 23250422]
[44]
Davis PE, Peters JM, Krueger DA, Sahin M. Tuberous sclerosis: A new frontier in targeted treatment of autism. Neurotherapeutics 2015; 12(3): 572-83.
[http://dx.doi.org/10.1007/s13311-015-0359-5] [PMID: 25986747]
[45]
Jeste SS, Sahin M, Bolton P, Ploubidis GB, Humphrey A. Characterization of autism in young children with tuberous sclerosis complex. J Child Neurol 2008; 23(5): 520-5.
[http://dx.doi.org/10.1177/0883073807309788] [PMID: 18160549]
[46]
Guy J, Cheval H, Selfridge J, Bird A. The role of MeCP2 in the brain. Annu Rev Cell Dev Biol 2011; 27(1): 631-52.
[http://dx.doi.org/10.1146/annurev-cellbio-092910-154121] [PMID: 21721946]
[47]
Samaco RC, Nagarajan RP, Braunschweig D, LaSalle JM. Multiple pathways regulate MeCP2 expression in normal brain development and exhibit defects in autism-spectrum disorders. Hum Mol Genet 2004; 13(6): 629-39.
[http://dx.doi.org/10.1093/hmg/ddh063] [PMID: 14734626]
[48]
Sztainberg Y, Chen HM, Swann JW, et al. Reversal of phenotypes in MECP2 duplication mice using genetic rescue or antisense oligonucleotides. Nature 2015; 528(7580): 123-6.
[http://dx.doi.org/10.1038/nature16159] [PMID: 26605526]
[49]
Tillotson R, Selfridge J, Koerner MV, et al. Radically truncated MeCP2 rescues Rett syndrome-like neurological defects. Nature 2017; 550(7676): 398-401.
[http://dx.doi.org/10.1038/nature24058] [PMID: 29019980]
[50]
Krishnan V, Stoppel DC, Nong Y, et al. Autism gene Ube3a and seizures impair sociability by repressing VTA Cbln1. Nature 2017; 543(7646): 507-12.
[http://dx.doi.org/10.1038/nature21678] [PMID: 28297715]
[51]
Hirai H, Pang Z, Bao D, et al. Cbln1 is essential for synaptic integrity and plasticity in the cerebellum. Nat Neurosci 2005; 8(11): 1534-41.
[http://dx.doi.org/10.1038/nn1576] [PMID: 16234806]
[52]
Meng L, Ward AJ, Chun S, Bennett CF, Beaudet AL, Rigo F. Towards a therapy for Angelman syndrome by targeting a long non-coding RNA. Nature 2015; 518(7539): 409-12.
[http://dx.doi.org/10.1038/nature13975] [PMID: 25470045]
[53]
Wang H. Fragile X mental retardation protein: From autism to neurodegenerative disease. Front Cell Neurosci 2015; 9: 43.
[http://dx.doi.org/10.3389/fncel.2015.00043] [PMID: 25729352]
[54]
Sethna F, Moon C, Wang H. From FMRP function to potential therapies for fragile X syndrome. Neurochem Res 2014; 39(6): 1016-31.
[http://dx.doi.org/10.1007/s11064-013-1229-3] [PMID: 24346713]
[55]
Jansen A, Dieleman GC, Smit AB, et al. Gene-set analysis shows association between FMRP targets and autism spectrum disorder. Eur J Hum Genet 2017; 25(7): 863-8.
[http://dx.doi.org/10.1038/ejhg.2017.55] [PMID: 28422133]
[56]
Shitik EM, Velmiskina AA, Dolskiy AA, Yudkin DV. Reactivation of FMR1 gene expression is a promising strategy for fragile X syndrome therapy. Gene Ther 2020; 27(6): 247-53.
[http://dx.doi.org/10.1038/s41434-020-0141-0] [PMID: 32203197]
[57]
Xie N, Gong H, Suhl JA, Chopra P, Wang T, Warren ST. Reactivation of FMR1 by CRISPR/Cas9-mediated deletion of the expanded CGG-repeat of the fragile X chromosome. PLoS One 2016; 11(10): e0165499.
[http://dx.doi.org/10.1371/journal.pone.0165499] [PMID: 27768763]
[58]
Novarino G, El-Fishawy P, Kayserili H, et al. Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. Science 2012; 338(6105): 394-7.
[http://dx.doi.org/10.1126/science.1224631] [PMID: 22956686]
[59]
Tărlungeanu DC, Deliu E, Dotter CP, et al. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell 2016; 167(6): 1481-1494.e18.
[http://dx.doi.org/10.1016/j.cell.2016.11.013] [PMID: 27912058]
[60]
Fernandez BA, Roberts W, Chung B, et al. Phenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder. J Med Genet 2010; 47(3): 195-203.
[http://dx.doi.org/10.1136/jmg.2009.069369] [PMID: 19755429]
[61]
Qu Y, Liu Y, Noor AF, Tran J, Li R. Characteristics and advantages of adeno-associated virus vector-mediated gene therapy for neurodegenerative diseases. Neural Regen Res 2019; 14(6): 931-8.
[http://dx.doi.org/10.4103/1673-5374.250570] [PMID: 30761996]
[62]
Rafii MS, Baumann TL, Bakay RAE, et al. A phase1 study of stereotactic gene delivery of AAV2-NGF for Alzheimer’s disease. Alzheimers Dement 2014; 10(5): 571-81.
[http://dx.doi.org/10.1016/j.jalz.2013.09.004] [PMID: 24411134]
[63]
Dobrowsky T, Gianni D, Pieracci J, Suh J. AAV manufacturing for clinical use: Insights on current challenges from the upstream process perspective. Curr Opin Biomed Eng 2021; 20: 100353.
[http://dx.doi.org/10.1016/j.cobme.2021.100353]
[64]
Lugin ML, Lee RT, Kwon YJ. Synthetically engineered adeno-associated virus for efficient, safe, and versatile gene therapy applications. ACS Nano 2020; 14(11): 14262-83.
[http://dx.doi.org/10.1021/acsnano.0c03850] [PMID: 33073995]
[65]
Al-Zaidy SA, Kolb SJ, Lowes L, et al. AVXS-101 (onasemnogene abeparvovec) for SMA1: Comparative study with a prospective natural history cohort. J Neuromuscul Dis 2019; 6(3): 307-17.
[http://dx.doi.org/10.3233/JND-190403] [PMID: 31381526]
[66]
Dabbous O, Maru B, Jansen JP, et al. Survival, motor function, and motor milestones: Comparison of AVXS-101 relative to nusinersen for the treatment of infants with spinal muscular atrophy type 1. Adv Ther 2019; 36(5): 1164-76.
[http://dx.doi.org/10.1007/s12325-019-00923-8] [PMID: 30879249]
[67]
Anderson IM, Haddad PM, Scott J. Bipolar disorder. BMJ 2012; 345(dec27 3): e8508.
[http://dx.doi.org/10.1136/bmj.e8508] [PMID: 23271744]
[68]
Santos R, Linker SB, Stern S, et al. Deficient LEF1 expression is associated with lithium resistance and hyperexcitability in neurons derived from bipolar disorder patients. Mol Psychiatry 2021; 26(6): 2440-56.
[http://dx.doi.org/10.1038/s41380-020-00981-3] [PMID: 33398088]
[69]
Fortinguerra S, Sorrenti V, Giusti P, Zusso M, Buriani A. Pharmacogenomic characterization in bipolar spectrum disorders. Pharmaceutics 2019; 12(1): 13.
[http://dx.doi.org/10.3390/pharmaceutics12010013] [PMID: 31877761]
[70]
Chen DT, Jiang X, Akula N, et al. Genome-wide association study meta-analysis of European and Asian-ancestry samples identifies three novel loci associated with bipolar disorder. Mol Psychiatry 2013; 18(2): 195-205.
[http://dx.doi.org/10.1038/mp.2011.157] [PMID: 22182935]
[71]
Ferreira MA, O’Donovan MC, Meng YA, et al. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet 2008; 40(9): 1056-8.
[http://dx.doi.org/10.1038/ng.209] [PMID: 18711365]
[72]
Mühleisen TW, Leber M, Schulze TG, et al. Genome-wide association study reveals two new risk loci for bipolar disorder. Nat Commun 2014; 5(1): 3339.
[http://dx.doi.org/10.1038/ncomms4339] [PMID: 24618891]
[73]
Smith KR, Kopeikina KJ, Fawcett-Patel JM, et al. Psychiatric risk factor ANK3/ankyrin-G nanodomains regulate the structure and function of glutamatergic synapses. Neuron 2014; 84(2): 399-415.
[http://dx.doi.org/10.1016/j.neuron.2014.10.010] [PMID: 25374361]
[74]
Zhou D, Lambert S, Malen PL, Carpenter S, Boland LM, Bennett V. AnkyrinG is required for clustering of voltage-gated Na channels at axon initial segments and for normal action potential firing. J Cell Biol 1998; 143(5): 1295-304.
[http://dx.doi.org/10.1083/jcb.143.5.1295] [PMID: 9832557]
[75]
Durak O, de Anda FC, Singh KK, et al. Ankyrin-G regulates neurogenesis and Wnt signaling by altering the subcellular localization of β-catenin. Mol Psychiatry 2015; 20(3): 388-97.
[http://dx.doi.org/10.1038/mp.2014.42] [PMID: 24821222]
[76]
Chen HM, DeLong CJ, Bame M, et al. Transcripts involved in calcium signaling and telencephalic neuronal fate are altered in induced pluripotent stem cells from bipolar disorder patients. Transl Psychiatry 2014; 4(3): e375-5.
[http://dx.doi.org/10.1038/tp.2014.12] [PMID: 25116795]
[77]
Madison JM, Zhou F, Nigam A, et al. Characterization of bipolar disorder patient-specific induced pluripotent stem cells from a family reveals neurodevelopmental and mRNA expression abnormalities. Mol Psychiatry 2015; 20(6): 703-17.
[http://dx.doi.org/10.1038/mp.2015.7] [PMID: 25733313]
[78]
Misztal K, Brozko N, Nagalski A, et al. TCF7L2 mediates the cellular and behavioral response to chronic lithium treatment in animal models. Neuropharmacology 2017; 113(Pt A): 490-501.
[http://dx.doi.org/10.1016/j.neuropharm.2016.10.027] [PMID: 27793772]
[79]
Suske G. The Sp-family of transcription factors. Gene 1999; 238(2): 291-300.
[http://dx.doi.org/10.1016/S0378-1119(99)00357-1] [PMID: 10570957]
[80]
Ramos B, Gaudillière B, Bonni A, Gill G. Transcription factor Sp4 regulates dendritic patterning during cerebellar maturation. Proc Natl Acad Sci USA 2007; 104(23): 9882-7.
[http://dx.doi.org/10.1073/pnas.0701946104] [PMID: 17535924]
[81]
Zhou X, Tang W, Greenwood TA, et al. Transcription factor SP4 is a susceptibility gene for bipolar disorder. PLoS One 2009; 4(4): e5196.
[http://dx.doi.org/10.1371/journal.pone.0005196] [PMID: 19401786]
[82]
Pinacho R, Villalmanzo N, Lalonde J, et al. The transcription factor SP4 is reduced in postmortem cerebellum of bipolar disorder subjects: Control by depolarization and lithium. Bipolar Disord 2011; 13(5-6): 474-85.
[http://dx.doi.org/10.1111/j.1399-5618.2011.00941.x] [PMID: 22017217]
[83]
Pinacho R, Valdizán EM, Pilar-Cuellar F, et al. Increased SP4 and SP1 transcription factor expression in the postmortem hippocampus of chronic schizophrenia. J Psychiatr Res 2014; 58: 189-96.
[http://dx.doi.org/10.1016/j.jpsychires.2014.08.006] [PMID: 25175639]
[84]
Gogos JA, Karayiorgou M. “Targeting” schizophrenia in mice. Am J Med Genet 2001; 105(1): 50-2.
[http://dx.doi.org/10.1002/1096-8628(20010108)105:1<50::AIDAJMG1058>3.0.CO;2-5] [PMID: 11424997]
[85]
Perkovic MN, Erjavec GN, Strac DS, Uzun S, Kozumplik O, Pivac N. Theranostic biomarkers for schizophrenia. Int J Mol Sci 2017; 18(4): 733.
[http://dx.doi.org/10.3390/ijms18040733] [PMID: 28358316]
[86]
Weickert CS, Weickert TW, Pillai A, Buckley PF. Biomarkers in schizophrenia: A brief conceptual consideration. Dis Markers 2013; 35(1): 3-9.
[http://dx.doi.org/10.1155/2013/510402] [PMID: 24167344]
[87]
Gaebel W, Zielasek J. Schizophrenia in 2020: Trends in diagnosis and therapy. Psychiatry Clin Neurosci 2015; 69(11): 661-73.
[http://dx.doi.org/10.1111/pcn.12322] [PMID: 26011091]
[88]
Balu DT. The NMDA receptor and schizophrenia: From pathophysiology to treatment. Adv Pharmacol 2016; 76: 351-82.
[http://dx.doi.org/10.1016/bs.apha.2016.01.006] [PMID: 27288082]
[89]
Domino EF, Luby ED. Phencyclidine/schizophrenia: One view toward the past, the other to the future. Schizophr Bull 2012; 38(5): 914-9.
[http://dx.doi.org/10.1093/schbul/sbs011] [PMID: 22390879]
[90]
Meltzer HY, Rajagopal L, Huang M, Oyamada Y, Kwon S, Horiguchi M. Translating the N-methyl-D-aspartate receptor antagonist model of schizophrenia to treatments for cognitive impairment in schizophrenia. Int J Neuropsychopharmacol 2013; 16(10): 2181-94.
[http://dx.doi.org/10.1017/S1461145713000928] [PMID: 24099265]
[91]
Greene R. Circuit analysis of NMDAR hypofunction in the hippocampus, in vitro, and psychosis of schizophrenia. Hippocampus 2001; 11(5): 569-77.
[http://dx.doi.org/10.1002/hipo.1072] [PMID: 11732709]
[92]
Byne W, Hazlett EA, Buchsbaum MS, Kemether E. The thalamus and schizophrenia: Current status of research. Acta Neuropathol 2009; 117(4): 347-68.
[http://dx.doi.org/10.1007/s00401-008-0404-0] [PMID: 18604544]
[93]
Yasuda K, Hayashi Y, Yoshida T, et al. Schizophrenia-like phenotypes in mice with NMDA receptor ablation in intralaminar thalamic nucleus cells and gene therapy-based reversal in adults. Transl Psychiatry 2017; 7(2): e1047-7.
[http://dx.doi.org/10.1038/tp.2017.19] [PMID: 28244984]
[94]
Cao T, Zhen XC. Dysregulation of miRNA and its potential therapeutic application in schizophrenia. CNS Neurosci Ther 2018; 24(7): 586-97.
[http://dx.doi.org/10.1111/cns.12840] [PMID: 29529357]
[95]
Nadim WD, Simion V, Bénédetti H, Pichon C, Baril P, Morisset-Lopez S. MicroRNAs in neurocognitive dysfunctions: New molecular targets for pharmacological treatments? Curr Neuropharmacol 2017; 15(2): 260-75.
[http://dx.doi.org/10.2174/1570159X14666160709001441] [PMID: 27396304]
[96]
Rajman M, Schratt G. MicroRNAs in neural development: From master regulators to fine-tuners. Development 2017; 144(13): 2310-22.
[http://dx.doi.org/10.1242/dev.144337] [PMID: 28676566]
[97]
Im H-I, Kenny PJ. MicroRNAs in neuronal function and dysfunction. Trends Neurosci 2012; 35(5): 325-34.
[http://dx.doi.org/10.1016/j.tins.2012.01.004] [PMID: 22436491]
[98]
Mahmoudi E, Cairns MJ. MiR-137: An important player in neural development and neoplastic transformation. Mol Psychiatry 2017; 22(1): 44-55.
[http://dx.doi.org/10.1038/mp.2016.150] [PMID: 27620842]
[99]
Paul S, Reyes PR, Garza BS, Sharma A. MicroRNAs and child neuropsychiatric disorders: A brief review. Neurochem Res 2020; 45(2): 232-40.
[http://dx.doi.org/10.1007/s11064-019-02917-y] [PMID: 31773374]
[100]
Gizak A, Duda P, Pielka E, McCubrey JA, Rakus D. GSK3 and miRNA in neural tissue: From brain development to neurodegenerative diseases. Biochim Biophys Acta Mol Cell Res 2020; 1867(7): 118696.
[http://dx.doi.org/10.1016/j.bbamcr.2020.118696] [PMID: 32165184]
[101]
Ching A-S, Ahmad-Annuar A. A perspective on the role of microRNA-128 regulation in mental and behavioral disorders. Front Cell Neurosci 2015; 9: 465.
[http://dx.doi.org/10.3389/fncel.2015.00465] [PMID: 26696825]
[102]
González-Castro TB, Hernández-Díaz Y, Juárez-Rojop IE, et al. The role of C957T, TaqI and Ser311Cys polymorphisms of the DRD2 gene in schizophrenia: Systematic review and meta-analysis. Behav Brain Funct 2016; 12(1): 29.
[http://dx.doi.org/10.1186/s12993-016-0114-z] [PMID: 27829443]
[103]
Hussain MS, Siddiqui SA, Mondal S, et al. Association of DRD2 gene polymorphisms with schizophrenia in the young Bangladeshi population: A pilot study. Heliyon 2020; 6(10): e05125.
[http://dx.doi.org/10.1016/j.heliyon.2020.e05125] [PMID: 33043160]
[104]
Sumiyoshi T, Kunugi H, Nakagome K. Serotonin and dopamine receptors in motivational and cognitive disturbances of schizophrenia. Front Neurosci 2014; 8: 395.
[http://dx.doi.org/10.3389/fnins.2014.00395] [PMID: 25538549]
[105]
Jönsson EG, Sillén A, Vares M, Ekholm B, Terenius L, Sedvall GC. Dopamine D2 receptor gene Ser311Cys variant and schizophrenia: Association study and meta-analysis. Am J Med Genet B Neuropsychiatr Genet 2003; 119B(1): 28-34.
[http://dx.doi.org/10.1002/ajmg.b.20004] [PMID: 12707934]
[106]
Glatt SJ, Faraone SV, Tsuang MT. Meta-analysis identifies an association between the dopamine D2 receptor gene and schizophrenia. Mol Psychiatry 2003; 8(11): 911-5.
[http://dx.doi.org/10.1038/sj.mp.4001321] [PMID: 14593428]
[107]
Mitra R, Ferguson D, Sapolsky RM. SK2 potassium channel overexpression in basolateral amygdala reduces anxiety, stress-induced corticosterone secretion and dendritic arborization. Mol Psychiatry 2009; 14(9): 847-855, 827.
[http://dx.doi.org/10.1038/mp.2009.9] [PMID: 19204724]
[108]
Fuentes CM, Schaffer DV. Adeno-associated virus-mediated delivery of CRISPR-Cas9 for genome editing in the central nervous system. Curr Opin Biomed Eng 2018; 7: 33-41.
[http://dx.doi.org/10.1016/j.cobme.2018.08.003] [PMID: 34046535]
[109]
Kos A, Aschrafi A, Nadif KN. The multifarious hippocampal functions of microRNA-137. Neuroscientist 2016; 22(5): 440-6.
[http://dx.doi.org/10.1177/1073858415608356] [PMID: 26396150]
[110]
Murlidharan G, Sakamoto K, Rao L, et al. CNS-restricted transduction and CRISPR/Cas9-mediated gene deletion with an engineered AAV vector. Mol Ther Nucleic Acids 2016; 5(7): e338.
[http://dx.doi.org/10.1038/mtna.2016.49] [PMID: 27434683]
[111]
Van SJX, de Candia T. Meta-analytic evidence for familial coaggregation of schizophrenia and bipolar disorder. Arch Gen Psychiatry 2009; 66(7): 748-55.
[http://dx.doi.org/10.1001/archgenpsychiatry.2009.64] [PMID: 19581566]
[112]
Teng X, Aouacheria A, Lionnard L, et al. KCTD: A new gene family involved in neurodevelopmental and neuropsychiatric disorders. CNS Neurosci Ther 2019; 25(7): 887-902.
[http://dx.doi.org/10.1111/cns.13156] [PMID: 31197948]
[113]
Sibille E, Wang Y, Joeyen-Waldorf J, et al. A molecular signature of depression in the amygdala. Am J Psychiatry 2009; 166(9): 1011-24.
[http://dx.doi.org/10.1176/appi.ajp.2009.08121760] [PMID: 19605536]
[114]
Benes FM. Amygdalocortical circuitry in schizophrenia: From circuits to molecules. Neuropsychopharmacology 2010; 35(1): 239-57.
[http://dx.doi.org/10.1038/npp.2009.116] [PMID: 19727065]
[115]
Cathomas F, Stegen M, Sigrist H, et al. Altered emotionality and neuronal excitability in mice lacking KCTD12, an auxiliary subunit of GABAB receptors associated with mood disorders. Transl Psychiatry 2015; 5(2): e510-0.
[http://dx.doi.org/10.1038/tp.2015.8] [PMID: 25689571]
[116]
Chen N, Bao Y, Xue Y, et al. Meta-analyses of RELN variants in neuropsychiatric disorders. Behav Brain Res 2017; 332: 110-9.
[http://dx.doi.org/10.1016/j.bbr.2017.05.028] [PMID: 28506622]
[117]
Guidotti A, Grayson DR, Caruncho HJ. Epigenetic RELN dysfunction in schizophrenia and related neuropsychiatric disorders. Front Cell Neurosci 2016; 10: 89.
[http://dx.doi.org/10.3389/fncel.2016.00089] [PMID: 27092053]
[118]
Wang Z, Hong Y, Zou L, et al. Reelin gene variants and risk of autism spectrum disorders: An integrated meta-analysis. Am J Med Genet B Neuropsychiatr Genet 2014; 165B(2): 192-200.
[http://dx.doi.org/10.1002/ajmg.b.32222] [PMID: 24453138]
[119]
Ishii K, Kubo KI, Nakajima K. Reelin and neuropsychiatric disorders. Front Cell Neurosci 2016; 10: 229.
[http://dx.doi.org/10.3389/fncel.2016.00229] [PMID: 27803648]
[120]
Liu X-Y, Li M, Yang S-Y, Su B, Yin L-D. Association of RELN SNP rs7341475 with schizophrenia in the Chinese population. Dongwuxue Yanjiu 2011; 32(5): 499-503.
[http://dx.doi.org/10.3724/SP.J.1141.2011.05499] [PMID: 22006801]
[121]
Ben-David E, Shifman S, Shifman S. Further investigation of the association between rs7341475 and rs17746501 and schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2010; 153B(6): 1244-7.
[http://dx.doi.org/10.1002/ajmg.b.31093] [PMID: 20468075]
[122]
Paquette AJ, Perez SE, Anderson DJ. Constitutive expression of the neuron-restrictive silencer factor (NRSF)/REST in differentiating neurons disrupts neuronal gene expression and causes axon pathfinding errors in vivo. Proc Natl Acad Sci USA 2000; 97(22): 12318-23.
[http://dx.doi.org/10.1073/pnas.97.22.12318] [PMID: 11050251]
[123]
Thompson R, Chan C. NRSF and its epigenetic effectors: New treatments for neurological disease. Brain Sci 2018; 8(12): 226.
[http://dx.doi.org/10.3390/brainsci8120226] [PMID: 30572571]
[124]
Peter CJ, Saito A, Hasegawa Y, et al. In vivo epigenetic editing of Sema6a promoter reverses transcallosal dysconnectivity caused by C11orf46/Arl14ep risk gene. Nat Commun 2019; 10(1): 4112.
[http://dx.doi.org/10.1038/s41467-019-12013-y] [PMID: 31511512]
[125]
Stoekenbroek RM, Lambert G, Cariou B, Hovingh GK. Inhibiting PCSK9 - biology beyond LDL control. Nat Rev Endocrinol 2018; 15(1): 52-62.
[http://dx.doi.org/10.1038/s41574-018-0110-5] [PMID: 30367179]
[126]
Lee JS, Rosoff D, Luo A, et al. PCSK9 is increased in cerebrospinal fluid of individuals with alcohol use disorder. Alcohol Clin Exp Res 2019; 43(6): 1163-9.
[PMID: 30933362]
[127]
Fitzgerald K, White S, Borodovsky A, et al. A highly durable RNAi therapeutic inhibitor of PCSK9. N Engl J Med 2017; 376(1): 41-51.
[http://dx.doi.org/10.1056/NEJMoa1609243] [PMID: 27959715]
[128]
Kosmas CE, Muñoz EA, Sourlas A, et al. Inclisiran: A new promising agent in the management of hypercholesterolemia. Diseases 2018; 6(3): 63.
[http://dx.doi.org/10.3390/diseases6030063] [PMID: 30011788]
[129]
Hoyer D, Dev KK. RNA interference as a therapeutic strategy for treating CNS disorders. Drug Discov Today Ther Strateg 2006; 3(4): 451-6.
[http://dx.doi.org/10.1016/j.ddstr.2006.10.008] [PMID: 32288775]
[130]
Naoi M, Riederer P, Maruyama W. Modulation of monoamine oxidase (MAO) expression in neuropsychiatric disorders: Genetic and environmental factors involved in type A MAO expression. J Neural Transm (Vienna) 2016; 123(2): 91-106.
[http://dx.doi.org/10.1007/s00702-014-1362-4] [PMID: 25604428]
[131]
Shih JC, Wu JB, Chen K. Transcriptional regulation and multiple functions of MAO genes. J Neural Transm (Vienna) 2011; 118(7): 979-86.
[http://dx.doi.org/10.1007/s00702-010-0562-9] [PMID: 21359973]
[132]
Nagatsu T. Progress in monoamine oxidase (MAO) research in relation to genetic engineering. Neurotoxicology 2004; 25(1-2): 11-20.
[http://dx.doi.org/10.1016/S0161-813X(03)00085-8] [PMID: 14697876]
[133]
Sun Y, Zhang J, Yuan Y, Yu X, Shen Y, Xu Q. Study of a possible role of the monoamine oxidase A (MAOA) gene in paranoid schizophrenia among a Chinese population. Am J Med Genet B Neuropsychiatr Genet 2012; 159B(1): 104-11.
[http://dx.doi.org/10.1002/ajmg.b.32009] [PMID: 22162429]
[134]
Rivera M, Gutiérrez B, Molina E, et al. High-activity variants of the uMAOA polymorphism increase the risk for depression in a large primary care sample. Am J Med Genet B Neuropsychiatr Genet 2009; 150B(3): 395-402.
[http://dx.doi.org/10.1002/ajmg.b.30829] [PMID: 18626920]
[135]
Nelson RJ, Trainor BC. Neural mechanisms of aggression. Nat Rev Neurosci 2007; 8(7): 536-46.
[http://dx.doi.org/10.1038/nrn2174] [PMID: 17585306]
[136]
Kolla NJ, Matthews B, Wilson AA, et al. Lower monoamine oxidase-a total distribution volume in impulsive and violent male offenders with antisocial personality disorder and high psychopathic traits: An [11 C] Harmine positron emission tomography study. Neuropsychopharmacology 2015; 40(11): 2596-603.
[http://dx.doi.org/10.1038/npp.2015.106] [PMID: 26081301]
[137]
Jiang S, Xin R, Lin S, et al. Linkage studies between attention-deficit hyperactivity disorder and the monoamine oxidase genes. Am J Med Genet 2001; 105(8): 783-8.
[http://dx.doi.org/10.1002/ajmg.10098] [PMID: 11803531]
[138]
Cohen IL, Liu X, Lewis ME, et al. Autism severity is associated with child and maternal MAOA genotypes. Clin Genet 2011; 79(4): 355-62.
[http://dx.doi.org/10.1111/j.1399-0004.2010.01471.x] [PMID: 20573161]
[139]
Wang CC, Borchert A, Ugun-Klusek A, et al. Monoamine oxidase a expression is vital for embryonic brain development by modulating developmental apoptosis. J Biol Chem 2011; 286(32): 28322-30.
[http://dx.doi.org/10.1074/jbc.M111.241422] [PMID: 21697081]
[140]
Roberts RC. Schizophrenia in translation: Disrupted in schizophrenia (DISC1): Integrating clinical and basic findings. Schizophr Bull 2007; 33(1): 11-5.
[http://dx.doi.org/10.1093/schbul/sbl063] [PMID: 17138582]
[141]
Brandon NJ, Millar JK, Korth C, Sive H, Singh KK, Sawa A. Understanding the role of DISC1 in psychiatric disease and during normal development. J Neurosci 2009; 29(41): 12768-75.
[http://dx.doi.org/10.1523/JNEUROSCI.3355-09.2009] [PMID: 19828788]
[142]
Park Y-U, Jeong J, Lee H, et al. Disrupted-in-schizophrenia 1 (DISC1) plays essential roles in mitochondria in collaboration with Mitofilin. Proc Natl Acad Sci USA 2010; 107(41): 17785-90.
[http://dx.doi.org/10.1073/pnas.1004361107] [PMID: 20880836]
[143]
Kodama K, Katayama Y, Shoji Y, Nakashima H. The features and shortcomings for gene delivery of current non-viral carriers. Curr Med Chem 2006; 13(18): 2155-61.
[http://dx.doi.org/10.2174/092986706777935276] [PMID: 16918345]
[144]
Lin G, Li L, Panwar N, et al. Non-viral gene therapy using multifunctional nanoparticles: Status, challenges, and opportunities. Coord Chem Rev 2018; 374: 133-52.
[http://dx.doi.org/10.1016/j.ccr.2018.07.001]
[145]
Jayant RD, Sosa D, Kaushik A, et al. Current status of non-viral gene therapy for CNS disorders. Expert Opin Drug Deliv 2016; 13(10): 1433-45.
[http://dx.doi.org/10.1080/17425247.2016.1188802] [PMID: 27249310]
[146]
Roy I, Stachowiak MK, Bergey EJ. Nonviral gene transfection nanoparticles: Function and applications in the brain. Nanomedicine 2008; 4(2): 89-97.
[http://dx.doi.org/10.1016/j.nano.2008.01.002] [PMID: 18313990]
[147]
Katragadda CS, Choudhury PK, Murthy P. Nanoparticles as non-viral gene delivery vectors. Indian J Pharm Educ Res 2010; 44: 109-11.
[148]
Ragusa A, García I, Penadés S. Nanoparticles as nonviral gene delivery vectors. IEEE Trans Nanobiosci 2007; 6(4): 319-30.
[http://dx.doi.org/10.1109/TNB.2007.908996] [PMID: 18217625]
[149]
Hossain S, Akaike T, Chowdhury EH. Current approaches for drug delivery to central nervous system. Curr Drug Deliv 2010; 7(5): 389-97.
[http://dx.doi.org/10.2174/156720110793566245] [PMID: 20950269]
[150]
Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 2011; 29(4): 341-5.
[http://dx.doi.org/10.1038/nbt.1807] [PMID: 21423189]
[151]
Théry C, Boussac M, Véron P, et al. Proteomic analysis of dendritic cell-derived exosomes: A secreted subcellular compartment distinct from apoptotic vesicles. J Immunol 2001; 166(12): 7309-18.
[http://dx.doi.org/10.4049/jimmunol.166.12.7309] [PMID: 11390481]
[152]
Azmi AS, Bao B, Sarkar FH. Exosomes in cancer development, metastasis, and drug resistance: A comprehensive review. Cancer Metastasis Rev 2013; 32(3-4): 623-42.
[http://dx.doi.org/10.1007/s10555-013-9441-9] [PMID: 23709120]
[153]
Hwang DW, Son S, Jang J, et al. A brain-targeted rabies virus glycoprotein-disulfide linked PEI nanocarrier for delivery of neurogenic microRNA. Biomaterials 2011; 32(21): 4968-75.
[http://dx.doi.org/10.1016/j.biomaterials.2011.03.047] [PMID: 21489620]
[154]
Khatri N, Man H-Y. The autism and Angelman syndrome protein Ube3A/E6AP: The gene, E3 ligase ubiquitination targets and neurobiological functions. Front Mol Neurosci 2019; 12: 109.
[http://dx.doi.org/10.3389/fnmol.2019.00109] [PMID: 31114479]
[155]
Escamilla CO, Filonova I, Walker AK, et al. Kctd13 deletion reduces synaptic transmission via increased RhoA. Nature 2017; 551(7679): 227-31.
[http://dx.doi.org/10.1038/nature24470] [PMID: 29088697]
[156]
Lammert DB, Howell BW. RELN mutations in autism spectrum disorder. Front Cell Neurosci 2016; 10: 84.
[http://dx.doi.org/10.3389/fncel.2016.00084] [PMID: 27064498]
[157]
Araki K, Kuwano R, Morii K, et al. Structure and expression of human and rat D2 dopamine receptor genes. Neurochem Int 1992; 21(1): 91-8.
[http://dx.doi.org/10.1016/0197-0186(92)90071-X] [PMID: 1363862]
[158]
Dahoun T, Trossbach SV, Brandon NJ, Korth C, Howes OD. The impact of Disrupted-in-Schizophrenia 1 (DISC1) on the dopaminergic system: A systematic review. Transl Psychiatry 2017; 7(1): e1015-5.
[http://dx.doi.org/10.1038/tp.2016.282] [PMID: 28140405]
[159]
Shih JC, Thompson RF. Monoamine oxidase in neuropsychiatry and behavior. Am J Hum Genet 1999; 65(3): 593-8.
[http://dx.doi.org/10.1086/302562] [PMID: 10441564]
[160]
Kasahara K, Kawakami Y, Kiyono T, et al. Ubiquitin-proteasome system controls ciliogenesis at the initial step of axoneme extension. Nat Commun 2014; 5(1): 5081.
[http://dx.doi.org/10.1038/ncomms6081] [PMID: 25270598]

Rights & Permissions Print Cite
Article Metrics
8
© 2024 Bentham Science Publishers | Privacy Policy