Molecular basis for prospective pharmacological treatment strategies in intellectual disability syndromes

Developmental Neurobiology

Volumn 74, Issue 2, 2014, Pages 197-206

  Verpelli, Chiara ^a   Galimberti, Ivan ^b   Gomez Mancilla, Baltazar ^b   Sala, Carlo ^a,c  

^a UNIVERSITY OF MILAN   (Italy)

^b Arthritis and Bone Research   (Switzerland)

^c DEPARTMENT OF NEUROSURGERY   (Italy)

Author keywords

Autism; Intellectual disability; Synapses

Indexed keywords

ARTICLE; CYTOSKELETON; DENDRITIC SPINE; DISEASE SEVERITY; HUMAN; INTELLECTUAL IMPAIRMENT; MOLECULAR MECHANICS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN SYNTHESIS; SYNAPSE; X CHROMOSOME LINKED DISORDER;

AUTISM; INTELLECTUAL DISABILITY; SYNAPSES;

ANIMALS; GENETIC DISEASES, X-LINKED; HUMANS; INTELLECTUAL DISABILITY; NEURONS; SYNAPSES; SYNAPTIC TRANSMISSION; SYNDROME;

EID: 84891902101     PISSN: 19328451     EISSN: 10974695     Source Type: Journal    
DOI: 10.1002/dneu.22093     Document Type: Article

References (103)

1. Alarcón M, Abrahams BS, Stone JL, Duvall JA, Perederiy JV, Bomar JM, Sebat J, et al. 2008. Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene. Am J Hum Genet 82:150-159.
2. Arking DE, Cutler DJ, Brune CW, Teslovich TM, West K, Ikeda M, Rea A, et al. 2008. A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism. Am J Hum Genet 82:160-164.
3. Bagni C, Greenough WT. 2005. From mRNP trafficking to spine dysmorphogenesis: The roots of fragile X syndrome. Nat Rev Neurosci 6:376-387.
4. Bahi N, Friocourt G, Carrie A, Graham ME, Weiss JL, Chafey P, Fauchereau F, et al. 2003. IL1 receptor accessory protein like, a protein involved in X-linked mental retardation, interacts with Neuronal Calcium Sensor-1 and regulates exocytosis. Hum Mol Genet 12:1415-1425.
5. Bakkaloglu B, O'Roak BJ, Louvi A, Gupta AR, Abelson JF, Morgan TM, Chawarska K, et al. 2008. Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders. Am J Hum Genet 82:165-173.
6. Bassell GJ, Warren ST. 2008. Fragile X syndrome: Loss of local mRNA regulation alters synaptic development and function. Neuron 60:201-214.
7. Baudouin SJ, Gaudias J, Gerharz S, Hatstatt L, Zhou K, Punnakkal P, Tanaka KF, et al. 2012. Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism. Science 338:128-132.
8. Bauman ML, Kemper TL, Arin DM. 1995. Pervasive neuroanatomic abnormalities of the brain in three cases of Rett's syndrome. Neurology 45:1581-1586.
9. Bear MF. 2005. Therapeutic implications of the mGluR theory of fragile X mental retardation. Genes Brain Behav 4:393-398.
10. Blanpied TA, Ehlers MD. 2004. Microanatomy of dendritic spines: Emerging principles of synaptic pathology in psychiatric and neurological disease. Biol Psychiatry 55:1121-1127.
11. Catterall WA. 2000. From ionic currents to molecular mechanisms: The structure and function of voltage-gated sodium channels. Neuron 26:13-25.
12. Centonze D, Rossi S, Mercaldo V, Napoli I, Ciotti MT, De Chiara V, Musella A, et al. 2008. Abnormal striatal GABA transmission in the mouse model for the fragile X syndrome. Biol Psychiatry 63:963-973.
13. Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, Zoghbi HY. 2008. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320:1224-1229.
14. Chao HT, Zoghbi HY, Rosenmund C. 2007. MeCP2 controls excitatory synaptic strength by regulating glutamatergic synapse number. Neuron 56:58-65.
15. Chapleau CA, Calfa GD, Lane MC, Albertson AJ, Larimore JL, Kudo S, Armstrong DL, et al. 2009. Dendritic spine pathologies in hippocampal pyramidal neurons from Rett syndrome brain and after expression of Rett-associated MECP2 mutations. Neurobiol Dis 35:219-233.
16. Chih B, Engelman H, Scheiffele P. 2005. Control of excitatory and inhibitory synapse formation by neuroligins. Science 307:1324-1328.
17. Chocholska S, Rossier E, Barbi G, Kehrer-Sawatzki H. 2006. Molecular cytogenetic analysis of a familial interstitial deletion Xp22.2-22.3 with a highly variable phenotype in female carriers. Am J Med Genet A 140:604-610.
18. Chubykin AA, Atasoy D, Etherton MR, Brose N, Kavalali ET, Gibson JR, Südhof TC. 2007. Activity-dependent validation of excitatory versus inhibitory synapses by neuroligin-1 versus neuroligin-2. Neuron 54:919-931.
19. Colledge M, Snyder EM, Crozier RA, Soderling JA, Jin Y, Langeberg LK, Lu H, et al. 2003. Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression. Neuron 40:595-607.
20. Cook D, Nuro E, Murai KK. 2014. Increasing our understanding of human cognition through the study of fragile X syndrome. Dev. Neurobiol 74:147-177.
21. Dalva MB, McClelland AC, Kayser MS. 2007. Cell adhesion molecules: Signalling functions at the synapse. Nat Rev Neurosci 8:206-220.
22. Dani VS, Chang Q, Maffei A, Turrigiano GG, Jaenisch R, Nelson SB. 2005. Reduced cortical activity due to a shift in the balance between excitation and inhibition in a mouse model of Rett syndrome. Proc Natl Acad Sci U S A 102:12560-12565.
23. De Rubeis S, Bagni C. 2010. Fragile X mental retardation protein control of neuronal mRNA metabolism: Insights into mRNA stability. Mol Cell Neurosci 43:43-50.
24. Dean C, Dresbach T. 2006. Neuroligins and neurexins: Linking cell adhesion, synapse formation and cognitive function. Trends Neurosci 29:21-29.
25. Derecki NC, Cronk JC, Lu Z, Xu E, Abbott SB, Guyenet PG, Kipnis J. 2012. Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature 484:105-109.
26. Dölen G, Osterweil E, Rao BS, Smith GB, Auerbach BD, Chattarji S, Bear MF. 2007. Correction of fragile X syndrome in mice. Neuron 56:955-962.
27. Edbauer D, Neilson JR, Foster KA, Wang CF, Seeburg DP, Batterton MN, Tada T, et al. 2010. Regulation of synaptic structure and function by FMRP-associated microRNAs miR-125b and miR-132. Neuron 65:373-384.
28. Etherton M, Földy C, Sharma M, Tabuchi K, Liu X, Shamloo M, Malenka RC, et al. 2011. Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function. Proc Natl Acad Sci U S A 108:13764-13769.
29. Fonseca R, Vabulas RM, Hartl FU, Bonhoeffer T, Nägerl UV. 2006. A balance of protein synthesis and proteasome-dependent degradation determines the maintenance of LTP. Neuron 52:239-245.
30. Gambino F, Pavlowsky A, Béglé A, Dupont JL, Bahi N, Courjaret R, Gardette R, et al. 2007. IL1-receptor accessory protein-like 1 (IL1RAPL1), a protein involved in cognitive functions, regulates N-type Ca2+-channel and neurite elongation. Proc Natl Acad Sci U S A 104:9063-9068.
31. Govek EE, Newey SE, Akerman CJ, Cross JR, Van der Veken L, Van Aelst L. 2004. The X-linked mental retardation protein oligophrenin-1 is required for dendritic spine morphogenesis. Nat Neurosci 7:364-372.
32. Greer PL, Hanayama R, Bloodgood BL, Mardinly AR, Lipton DM, Flavell SW, Kim TK, et al. 2010. The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc. Cell 140:704-716.
33. Hamdan FF, Gauthier J, Araki Y, Lin DT, Yoshizawa Y, Higashi K, Park AR, et al. 2011. Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability. Am J Hum Genet 88:306-316.
34. Han S, Tai C, Westenbroek RE, Yu FH, Cheah CS, Potter GB, Rubenstein JL, et al. 2012. Autistic-like behaviour in Scn1a+/- mice and rescue by enhanced GABA-mediated neurotransmission. Nature 489:385-390.
35. Huber KM, Gallagher SM, Warren ST, Bear MF. 2002. Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc Natl Acad Sci U S A 99:7746-7750.
36. Jacquemont S, Curie A, des Portes V, Torrioli MG, Berry-Kravis E, Hagerman RJ, Ramos FJ, et al. 2011. Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056. Sci Transl Med 3:64ra61.
37. Jamain S, Quach H, Betancur C, Rastam M, Colineaux C, Gillberg IC, Soderstrom H, et al. 2003. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet 34:27-29.
38. Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, Copeland NG, et al. al. 2003. Mutant presenilins specifically elevate the levels of the 42 residue {beta}-amyloid peptide in vivo: Evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet 13:159-170.
39. Johnston MV, Blue ME, Naidu S. 2005. Rett syndrome and neuronal development. J Child Neurol 20:759-763.
40. Jones PL, Veenstra GJ, Wade PA, Vermaak D, Kass SU, Landsberger N, Strouboulis J, et al. 1998. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nat Genet 19:187-191.
41. Jourdi H, Hsu YT, Zhou M, Qin Q, Bi X, Baudry M. 2009. Positive AMPA receptor modulation rapidly stimulates BDNF release and increases dendritic mRNA translation. J Neurosci 29:8688-8697.
42. Khelfaoui M, Denis C, van Galen E, de Bock F, Schmitt A, Houbron C, Morice E, et al. 2007. Loss of X-linked mental retardation gene oligophrenin1 in mice impairs spatial memory and leads to ventricular enlargement and dendritic spine immaturity. J Neurosci 27:9439-9450.
43. Khelfaoui M, Pavlowsky A, Powell AD, Valnegri P, Cheong KW, Blandin Y, Passafaro M, et al. 2009. Inhibition of RhoA pathway rescues the endocytosis defects in Oligophrenin1 mouse model of mental retardation. Hum Mol Genet 18:2575-2583.
44. Kirov G, Gumus D, Chen W, Norton N, Georgieva L, Sari M, O'Donovan MC, et al. 2008. Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. Hum Mol Genet 17:458-465.
45. Kishino T, Lalande M, Wagstaff J. 1997. UBE3A/E6-AP mutations cause Angelman syndrome. Nat Genet 15:70-73.
46. Laggerbauer B, Ostareck D, Keidel EM, Ostareck-Lederer A, Fischer U. 2001. Evidence that fragile X mental retardation protein is a negative regulator of translation. Hum Mol Genet 10:329-338.
47. Laumonnier F, Bonnet-Brilhault F, Gomot M, Blanc R, David A, Moizard MP, Raynaud M, et al. 2004. 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 74:552-557.
48. Lawson-Yuen A, Saldivar JS, Sommer S, Picker J. 2008. Familial deletion within NLGN4 associated with autism and Tourette syndrome. Eur J Hum Genet 16:614-618.
49. Li H, Zhong X, Chau KF, Williams EC, Chang Q. 2011. Loss of activity-induced phosphorylation of MeCP2 enhances synaptogenesis, LTP and spatial memory. Nat Neurosci. 14:1001-1008
50. Li Z, Zhang Y, Ku L, Wilkinson KD, Warren ST, Feng Y. 2001. The fragile X mental retardation protein inhibits translation via interacting with mRNA. Nucleic Acids Res 29:2276-2283.
51. Lu R, Wang H, Liang Z, Ku L, O'Donnell WT, Li W, Warren ST, et al. 2004. The fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development. Proc Natl Acad Sci U S A 101:15201-15206.
52. Macarov M, Zeigler M, Newman JP, Strich D, Sury V, Tennenbaum A, Meiner V. 2007. Deletions of VCX-A and NLGN4: A variable phenotype including normal intellect. J Intellect Disabil Res 51:329-333.
53. Margolis SS, Salogiannis J, Lipton DM, Mandel-Brehm C, Wills ZP, Mardinly AR, Hu L, et al. 2010. EphB-mediated degradation of the RhoA GEF Ephexin5 relieves a developmental brake on excitatory synapse formation. Cell 143:442-455.
54. Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L, Skaug J, Shago M, et al. 2008. Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet 82:477-488.
55. Matson JL, Bamburg JW, Mayville EA, Pinkston J, Bielecki J, Kuhn D, Smalls Y, et al. 2000. Psychopharmacology and mental retardation: A 10 year review (1990-1999). Res Dev Disabil 21:263-296.
56. Matson JL, Bielecki J, Mayville SB, Matson ML. 2003. Psychopharmacology research for individuals with mental retardation: Methodological issues and suggestions. Res Dev Disabil 24:149-157.
57. Matson JL, Mahan S. 2010. Antipsychotic drug side effects for persons with intellectual disability. Res Dev Disabil 31:1570-1576.
58. Matsuura T, Sutcliffe JS, Fang P, Galjaard RJ, Jiang YH, Benton CS, Rommens JM, et al. 1997. De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome. Nat Genet 15:74-77.
59. Michalon A, Sidorov M, Ballard TM, Ozmen L, Spooren W, Wettstein JG, Jaeschke G, et al. 2012. Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice. Neuron 74:49-56.
60. Morrow EM, Yoo SY, Flavell SW, Kim TK, Lin Y, Hill RS, Mukaddes NM, et al. 2008. Identifying autism loci and genes by tracing recent shared ancestry. Science 321:218-223.
61. Muddashetty RS, Kelic S, Gross C, Xu M, Bassell GJ. 2007. Dysregulated metabotropic glutamate receptor-dependent translation of AMPA receptor and postsynaptic density-95 mRNAs at synapses in a mouse model of fragile X syndrome. J Neurosci 27:5338-5348.
62. Nadif Kasri N, Nakano-Kobayashi A, Malinow R, Li B, Van Aelst L. 2009. The Rho-linked mental retardation protein oligophrenin-1 controls synapse maturation and plasticity by stabilizing AMPA receptors. Genes Dev 23:1289-1302.
63. Nadif Kasri N, Van Aelst L. 2008. Rho-linked genes and neurological disorders. Pflugers Arch 455:787-797.
64. Nakano-Kobayashi A, Kasri NN, Newey SE, Van Aelst L. 2009. The Rho-linked mental retardation protein OPHN1 controls synaptic vesicle endocytosis via endophilin A1. Curr Biol 19:1133-1139.
65. Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, Bird A. 1998. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393:386-389.
66. Napoli I, Mercaldo V, Boyl PP, Eleuteri B, Zalfa F, De Rubeis S, Di Marino D, et al. 2008. The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP. Cell 134:1042-1054.
67. Ogiwara I, Miyamoto H, Morita N, Atapour N, Mazaki E, Inoue I, Takeuchi T, et al. 2007. Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation. J Neurosci 27:5903-5914.
68. Pavlowsky A, Gianfelice A, Pallotto M, Zanchi A, Vara H, Khelfaoui M, Valnegri P, et al. 2010. A postsynaptic signaling pathway that may account for the cognitive defect due to IL1RAPL1 mutation. Curr Biol 20:103-115.
69. Penzes P, Cahill ME, Jones KA, VanLeeuwen JE, Woolfrey KM. 2011. Dendritic spine pathology in neuropsychiatric disorders. Nat Neurosci 14:285-293.
70. Peñagarikano O, Abrahams BS, Herman EI, Winden KD, Gdalyahu A, Dong H, Sonnenblick LI, et al. 2011. Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits. Cell 147:235-246.
71. Pini G, Scusa MF, Congiu L, Benincasa A, Morescalchi P, Bottiglioni I, Di Marco P, et al. 2012. IGF1 as a potential treatment for rett syndrome: Safety assessment in six rett patients. Autism Res Treat 2012:679801.
72. Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan R, Conroy J, et al. 2010. Functional impact of global rare copy number variation in autism spectrum disorders. Nature 466:368-372.
73. Poliak S, Gollan L, Martinez R, Custer A, Einheber S, Salzer JL, Trimmer JS, et al. 1999. Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels. Neuron 24:1037-1047.
74. Poliak S, Salomon D, Elhanany H, Sabanay H, Kiernan B, Pevny L, Stewart CL, et al. 2003. Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1. J Cell Biol 162:1149-1160.
75. Powell AD, Gill KK, Saintot PP, Jiruska P, Chelly J, Billuart P, Jefferys JG. 2012. Rapid reversal of impaired inhibitory and excitatory transmission but not spine dysgenesis in a mouse model of mental retardation. J Physiol 590:763-776.
76. Rauch A, Hoyer J, Guth S, Zweier C, Kraus C, Becker C, Zenker M, et al. 2006. Diagnostic yield of various genetic approaches in patients with unexplained developmental delay or mental retardation. Am J Med Genet A 140:2063-2074.
77. Ricciardi S, Boggio EM, Grosso S, Lonetti G, Forlani G, Stefanelli G, Calcagno E, et al. 2011. Reduced AKT/mTOR signaling and protein synthesis dysregulation in a Rett syndrome animal model. Hum Mol Genet 20:1182-1196.
78. Ropers HH, Hamel BC. 2005. X-linked mental retardation. Nat Rev Genet 6:46-57.
79. Schutt J, Falley K, Richter D, Kreienkamp HJ, Kindler S. 2009. Fragile X mental retardation protein regulates the levels of scaffold proteins and glutamate receptors in postsynaptic densities. J Biol Chem 284:25479-25487.
80. Sutcliffe JS, Jiang YH, Galijaard RJ, Matsuura T, Fang P, Kubota T, Christian SL, et al. 1997. The E6-Ap ubiquitin-protein ligase (UBE3A) gene is localized within a narrowed Angelman syndrome critical region. Genome Res 7:368-377.
81. Südhof TC. 2008. Neuroligins and neurexins link synaptic function to cognitive disease. Nature 455:903-911.
82. Tabuchi K, Blundell J, Etherton MR, Hammer RE, Liu X, Powell CM, Südhof TC. 2007. A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science 318:71-76.
83. Talebizadeh Z, Lam DY, Theodoro MF, Bittel DC, Lushington GH, Butler MG. 2006. Novel splice isoforms for NLGN3 and NLGN4 with possible implications in autism. J Med Genet 43:e21.
84. Tao J, Hu K, Chang Q, Wu H, Sherman NE, Martinowich K, Klose RJ, et al. 2009. Phosphorylation of MeCP2 at Serine 80 regulates its chromatin association and neurological function. Proc Natl Acad Sci U S A 106:4882-4887.
85. Tropea D, Giacometti E, Wilson NR, Beard C, McCurry C, Fu DD, Flannery R, et al. 2009. Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. Proc Natl Acad Sci U S A 106:2029-2034.
86. Valnegri P, Khelfaoui M, Dorseuil O, Bassani S, Lagneaux C, Gianfelice A, Benfante R, et al. 2011a. A circadian clock in hippocampus is regulated by interaction between oligophrenin-1 and Rev-erbα. Nat Neurosci 14:1293-1301.
87. Valnegri P, Montrasio C, Brambilla D, Ko J, Passafaro M, Sala C. 2011b. The X-linked intellectual disability protein IL1RAPL1 regulates excitatory synapse formation by binding PTP{delta} and RhoGAP2. Hum Mol Genet 20:4797-4809.
88. Varoqueaux F, Aramuni G, Rawson RL, Mohrmann R, Missler M, Gottmann K, Zhang W, et al. 2006. Neuroligins determine synapse maturation and function. Neuron 51:741-754.
89. Vernes SC, Newbury DF, Abrahams BS, Winchester L, Nicod J, Groszer M, Alarcón M, et al. 2008. A functional genetic link between distinct developmental language disorders. N Engl J Med 359:2337-2345.
90. Vorstman JA, Ophoff RA. 2013. Genetic causes of developmental disorders. Curr Opin Neurol 26:128-136.
91. Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB, Cooper GM, Nord AS, et al. 2008. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320:539-543.
92. Winarni TI, Schneider A, Borodyanskara M, Hagerman RJ. 2012. Early intervention combined with targeted treatment promotes cognitive and behavioral improvements in young children with fragile x syndrome. Case Rep Genet 2012:280813.
93. Wollner DA, Catterall WA. 1986. Localization of sodium channels in axon hillocks and initial segments of retinal ganglion cells. Proc Natl Acad Sci U S A 83:8424-8428.
94. Yan J, Feng J, Schroer R, Li W, Skinner C, Schwartz CE, Cook EH, et al. 2008. Analysis of the neuroligin 4Y gene in patients with autism. Psychiatr Genet 18:204-207.
95. Yan Y, Yang D, Zarnowska ED, Du Z, Werbel B, Valliere C, Pearce RA, et al. 2005. Directed differentiation of dopaminergic neuronal subtypes from human embryonic stem cells. Stem Cells 23:781-790.
96. Yi JJ, Ehlers MD. 2005. Ubiquitin and protein turnover in synapse function. Neuron 47:629-632.
97. Yi JJ, Ehlers MD. 2007. Emerging roles for ubiquitin and protein degradation in neuronal function. Pharmacol Rev 59:14-39.
98. Yoshida T, Yasumura M, Uemura T, Lee SJ, Ra M, Taguchi R, Iwakura Y, et al. 2011. IL-1 receptor accessory protein-like 1 associated with mental retardation and autism mediates synapse formation by trans-synaptic interaction with protein tyrosine phosphatase {delta}. J Neurosci 31:13485-13499.
99. Yu FH, Mantegazza M, Westenbroek RE, Robbins CA, Kalume F, Burton KA, Spain WJ, et al. 2006. Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy. Nat Neurosci 9:1142-1149.
100. Zalfa F, Eleuteri B, Dickson KS, Mercaldo V, De Rubeis S, di Penta A, Tabolacci E, et al. 2007. A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability. Nat Neurosci 10:578-587.
101. Zalfa F, Giorgi M, Primerano B, Moro A, Di Penta A, Reis S, Oostra B, et al. 2003. The fragile X syndrome protein FMRP associates with BC1 RNA and regulates the translation of specific mRNAs at synapses. Cell 112:317-327.
102. Zhong X, Li H, Chang Q. 2012. MeCP2 Phosphorylation is required for modulating synaptic scaling through mGluR5. J Neurosci 32:12841-12847.
103. Zhou Z, Hong EJ, Cohen S, Zhao WN, Ho HY, Schmidt L, Chen WG, et al. 2006. Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation. Neuron 52:255-269.