Fragile X syndrome neurobiology translates into rational therapy

Drug Discovery Today

Volumn 19, Issue 4, 2014, Pages 510-519

  Braat, Sien ^a   Kooy, R Frank ^a  

^a UNIVERSITY OF ANTWERP   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR STIMULATING AGENT; 4 AMINOBUTYRIC ACID B RECEPTOR STIMULATING AGENT; ARBACLOFEN; ENDOCANNABINOID; GELATINASE B; GLYCOGEN SYNTHASE KINASE 3; MAVOGLURANT; METABOTROPIC RECEPTOR 1; METABOTROPIC RECEPTOR 5; MINOCYCLINE; MUSCARINIC RECEPTOR; RO 4917523; STX 107; UNCLASSIFIED DRUG; 4 AMINOBUTYRIC ACID RECEPTOR; METABOTROPIC RECEPTOR;

AUTISM; DENDRITIC SPINE; DRUG TARGETING; FRAGILE X SYNDROME; GABAERGIC SYSTEM; HUMAN; INTELLECTUAL IMPAIRMENT; NEUROBIOLOGY; NONHUMAN; PATHOPHYSIOLOGY; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); REVIEW; ANIMAL; METABOLISM; MOLECULARLY TARGETED THERAPY;

ANIMALS; ENDOCANNABINOIDS; FRAGILE X SYNDROME; HUMANS; MATRIX METALLOPROTEINASE 9; MOLECULAR TARGETED THERAPY; RECEPTORS, GABA; RECEPTORS, METABOTROPIC GLUTAMATE; RECEPTORS, MUSCARINIC;

EID: 84899579632     PISSN: 13596446     EISSN: 18785832     Source Type: Journal    
DOI: 10.1016/j.drudis.2014.01.013     Document Type: Review

References (101)

1. A.J.M.H. Verkerk 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 65 1991 905 914
2. M.R. Santoro et al. Molecular mechanisms of fragile X syndrome: a twenty-year perspective Annu. Rev. Pathol. 7 2012 219 245
3. S.M. McBride et al. Using Drosophila as a tool to identify pharmacological therapies for fragile X syndrome Drug Discov. Today: Technol. 10 2012 e129 e136
4. M.C. Ng et al. Behavioral and synaptic circuit features in a zebrafish model of fragile X syndrome PLoS One 8 2013 e51456
5. I. Heulens, and F. Kooy Fragile X syndrome: from gene discovery to therapy Front. Biosci. 16 2011 1211 1232
6. C.E. Bakker et al. Fmr1 knockout mice: a model to study fragile X mental retardation Cell 78 1994 23 33
7. H.L. Hinds et al. Tissue specific expression of FMR-1 provides evidence for a functional role in fragile X syndrome Nat. Genet. 3 1993 36 43
8. D. Devys et al. The FMR-1 protein is cytoplasmic, most abundant in neurons and appears normal in carriers of a fragile X premutation Nat. Genet. 4 1993 335 340
9. S.B. Christie et al. The FXG: a presynaptic fragile X granule expressed in a subset of developing brain circuits J. Neurosci. 29 2009 1514 1524
10. J.C. Darnell et al. FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism Cell 146 2011 247 261
11. D.E. Eberhart et al. The fragile X mental retardation protein is a ribonucleoprotein containing both nuclear localization and nuclear export signals Hum. Mol. Genet. 5 1996 1083 1091
12. K.M. Huber et al. Altered synaptic plasticity in a mouse model of fragile X mental retardation Proc. Natl. Acad. Sci. U. S. A. 99 2002 7746 7750
13. M.F. Bear et al. The mGluR theory of fragile X mental retardation Trends Neurosci. 27 2004 370 377
14. M. Qin et al. Postadolescent changes in regional cerebral protein synthesis: an in vivo study in the FMR1 null mouse J. Neurosci. 25 2005 5087 5095
15. G. Dolen et al. Correction of fragile X syndrome in mice Neuron 56 2007 955 962
16. G.K. Dhami, and S.S. Ferguson Regulation of metabotropic glutamate receptor signaling, desensitization and endocytosis Pharmacol. Ther. 111 2006 260 271
17. S.A. Hays et al. Altered neocortical rhythmic activity states in Fmr1 KO mice are due to enhanced mGluR5 signaling and involve changes in excitatory circuitry J. Neurosci. 31 2011 14223 14234
18. A.M. Thomas et al. Genetic reduction of group 1 metabotropic glutamate receptors alters select behaviors in a mouse model for fragile X syndrome Behav. Brain Res. 223 2011 310 321
19. D.D. Krueger, and M.F. Bear Toward fulfilling the promise of molecular medicine in fragile X syndrome Annu. Rev. Med. 62 2011 411 429
20. D.M. O'Leary et al. Selective mGluR5 antagonists MPEP and SIB-1893 decrease NMDA or glutamate-mediated neuronal toxicity through actions that reflect NMDA receptor antagonism Br. J. Pharmacol. 131 2000 1429 1437
21. F.M.S. de Vrij et al. Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice Neurobiol. Dis. 31 2008 127 132
22. M.F. Vinueza Veloz et al. The effect of an mGluR5 inhibitor on procedural memory and avoidance discrimination impairments in Fmr1 KO mice Genes Brain Behav. 11 2012 325 331
23. J. Levenga et al. AFQ056, a new mGluR5 antagonist for treatment of fragile X syndrome Neurobiol. Dis. 42 2011 311 317
24. A.S. Pop et al. Rescue of dendritic spine phenotype in Fmr1 KO mice with the mGluR5 antagonist AFQ056/Mavoglurant Psychopharmacology (Berl.) 2012 [Epub ahead of print]
25. I. Gantois et al. Chronic administration of AFQ056/Mavoglurant restores social behaviour in Fmr1 knockout mice Behav. Brain Res. 239 2013 72 79
26. A. Michalon et al. Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice Neuron 74 2012 49 56
27. A.M. Thomas et al. Group I metabotropic glutamate receptor antagonists alter select behaviors in a mouse model for fragile X syndrome Psychopharmacology (Berl.) 219 2012 47 58
28. C. Gross et al. Excess phosphoinositide 3-kinase subunit synthesis and activity as a novel therapeutic target in fragile X syndrome J. Neurosci. 30 2010 10624 10638
29. M.A. Mines, and R.S. Jope Glycogen synthase kinase-3: a promising therapeutic target for fragile x syndrome Front. Mol. Neurosci. 4 2011 35
30. C.T. Chiu, and D.M. Chuang Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders Pharmacol. Ther. 128 2010 281 304
31. W.W. Min et al. Elevated glycogen synthase kinase-3 activity in Fragile X mice: key metabolic regulator with evidence for treatment potential Neuropharmacology 56 2009 463 472
32. C.J. Yuskaitis et al. Lithium ameliorates altered glycogen synthase kinase-3 and behavior in a mouse model of fragile X syndrome Biochem. Pharmacol. 79 2010 632 646
33. W. Guo et al. Inhibition of GSK3beta improves hippocampus-dependent learning and rescues neurogenesis in a mouse model of fragile X syndrome Hum. Mol. Genet. 21 2012 681 691
34. A.V. Franklin et al. Glycogen synthase kinase-3 inhibitors reverse deficits in long-term potentiation and cognition in fragile X mice Biol. Psychiatry 75 2014 198 206
35. J.C. Darnell, and E. Klann The translation of translational control by FMRP: therapeutic targets for FXS Nat. Neurosci. 16 2013 1530 1536
36. L. Hou et al. Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression Neuron 51 2006 441 454
37. X. Wang et al. Activation of the extracellular signal-regulated kinase pathway contributes to the behavioral deficit of fragile x-syndrome J. Neurochem. 121 2012 672 679
38. N. Weng et al. Early-phase ERK activation as a biomarker for metabolic status in fragile X syndrome Am. J. Med. Genet. B Neuropsychiatr. Genet. 147 2008 1253 1257
39. S.H. Kim et al. Aberrant early-phase ERK inactivation impedes neuronal function in fragile X syndrome Proc. Natl. Acad. Sci. U. S. A. 105 2008 4429 4434
40. E.K. Osterweil et al. Hypersensitivity to mGluR5 and ERK1/2 leads to excessive protein synthesis in the hippocampus of a mouse model of fragile X syndrome J. Neurosci. 30 2010 15616 15627
41. E.K. Osterweil et al. Lovastatin corrects excess protein synthesis and prevents epileptogenesis in a mouse model of fragile X syndrome Neuron 77 2013 243 250
42. J.A. Ronesi, and K.M. Huber Homer interactions are necessary for metabotropic glutamate receptor-induced long-term depression and translational activation J. Neurosci. 28 2008 543 547
43. A. Sharma et al. Dysregulation of mTOR signaling in fragile X syndrome J. Neurosci. 30 2010 694 702
44. A. Busquets-Garcia et al. Targeting the Endocannabinoid system in the treatment of fragile X syndrome Nat Med. 19 2013 603 607
45. C. Gross et al. Therapeutic strategies in fragile X syndrome: dysregulated mGluR signaling and beyond Neuropsychopharmacology 37 2012 178 195
46. C. Gross, and G.J. Bassell Excess protein synthesis in FXS patient lymphoblastoid cells can be rescued with a p110beta-selective inhibitor Mol. Med. 18 2012 336 345
47. A. Bhattacharya et al. Genetic removal of p70 S6 kinase 1 corrects molecular, synaptic, and behavioral phenotypes in fragile X syndrome mice Neuron 76 2012 325 337
48. C.J. Westmark, and J.S. Malter FMRP mediates mGluR5-dependent translation of amyloid precursor protein PLoS Biol. 5 2007 e52
49. Y. Zhang et al. The tyrosine phosphatase STEP mediates AMPA receptor endocytosis after metabotropic glutamate receptor stimulation J. Neurosci. 28 2008 10561 10566
50. S.M. Goebel-Goody et al. Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model Genes Brain Behav. 11 2012 586 600
51. H.S. Hoe et al. The upside of APP at synapses CNS Neurosci. Ther. 18 2012 47 56
52. C.J. Westmark et al. Reversal of fragile X phenotypes by manipulation of AbetaPP/Abeta levels in Fmr1KO mice PLoS One 6 2011 e26549
53. S.M. Goebel-Goody et al. Therapeutic implications for striatal-enriched protein tyrosine phosphatase (STEP) in neuropsychiatric disorders Pharmacol. Rev. 64 2012 65 87
54. A. Matthys et al. Role of the 5-HT7 receptor in the central nervous system: from current status to future perspectives Mol. Neurobiol. 43 2011 228 253
55. L. Costa et al. Activation of 5-HT7 serotonin receptors reverses metabotropic glutamate receptor-mediated synaptic plasticity in wild-type and Fmr1 knockout mice, a model of Fragile X syndrome Biol. Psychiatry 72 2012 924 933
56. C. D'Hulst et al. The complexity of the GABA(A) receptor shapes unique pharmacological profiles Drug Discov. Today 14 2009 866 875
57. S.M. Paluszkiewicz et al. Fragile X syndrome: the GABAergic system and circuit dysfunction Dev. Neurosci. 33 2011 349 364
58. C. D'Hulst, and R.F. Kooy The GABA(A) receptor: a novel target for treatment of fragile X? Trends Neurosci. 30 2007 425 431
59. J.L. Olmos-Serrano et al. Defective GABAergic neurotransmission and pharmacological rescue of neuronal hyperexcitability in the amygdala in a mouse model of fragile X syndrome J. Neurosci. 30 2010 9929 9938
60. J.L. Olmos-Serrano et al. The GABA(A) Receptor agonist THIP ameliorates specific behavioral deficits in the mouse model of fragile X syndrome Dev. Neurosci. 33 2011 395 403
61. I. Heulens et al. Pharmacological treatment of fragile X syndrome with GABAergic drugs in a knockout mouse model Behav. Brain Res. 229 2012 244 249
62. N.G. Bowery et al. International Union of Pharmacology. XXXIII. Mammalian gamma-aminobutyric acid(B) receptors: structure and function Pharmacol. Rev. 54 2002 247 264
63. L.K. Pacey et al. Genetic deletion of regulator of G-protein signaling 4 (RGS4) rescues a subset of fragile X related phenotypes in the FMR1 knockout mouse Mol. Cell Neurosci. 46 2011 563 572
64. D.C. Adusei et al. Early developmental alterations in GABAergic protein expression in Fragile X knockout mice Neuropharmacology 59 2010 167 171
65. B receptor-mediated signaling reduces the susceptibility of fragile X knockout mice to audiogenic seizures Mol. Pharmacol. 76 2009 18 24
66. B receptor drug therapy in fragile X syndrome J. Pharmacol. Exp. Ther. 338 2011 897 905
67. C. Henderson et al. Reversal of disease-related pathologies in the fragile X mouse model by selective activation of GABA(B) receptors with arbaclofen Sci. Transl. Med. 4 2012 152ra128
68. M. Kano et al. Endocannabinoid-mediated control of synaptic transmission Physiol. Rev. 89 2009 309 380
69. L. Zhang, and B.E. Alger Enhanced endocannabinoid signaling elevates neuronal excitability in fragile X syndrome J. Neurosci. 30 2010 5724 5729
70. M. Maccarrone et al. Abnormal mGlu 5 receptor/endocannabinoid coupling in mice lacking FMRP and BC1 RNA Neuropsychopharmacology 35 2010 1500 1509
71. K.M. Jung et al. Uncoupling of the endocannabinoid signalling complex in a mouse model of fragile X syndrome Nat. Commun. 3 2012 1080
72. C. Portera-Cailliau Which comes first in fragile X syndrome, dendritic spine dysgenesis or defects in circuit plasticity? Neuroscientist 18 2012 28 44
73. H.J. Carlisle, and M.B. Kennedy Spine architecture and synaptic plasticity Trends Neurosci. 28 2005 182 187
74. M.L. Hayashi et al. Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice Proc. Natl. Acad. Sci. U. S. A. 104 2007 11489 11494
75. L.Y. Chen et al. Physiological activation of synaptic Rac > PAK (p-21 activated kinase) signaling is defective in a mouse model of fragile X syndrome J. Neurosci. 30 2010 10977 10984
76. M.L. Hayashi et al. Altered cortical synaptic morphology and impaired memory consolidation in forebrain-specific dominant-negative PAK transgenic mice Neuron 42 2004 773 787
77. B.M. Dolan et al. Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486 Proc. Natl. Acad. Sci. U. S. A. 110 2013 5671 5676
78. R.M. Eglen Muscarinic receptor subtypes in neuronal and non-neuronal cholinergic function Auton. Autacoid. Pharmacol. 26 2006 219 233
79. L.J. Volk et al. Multiple Gq-coupled receptors converge on a common protein synthesis-dependent long-term depression that is affected in fragile X syndrome mental retardation J. Neurosci. 27 2007 11624 11634
80. S. Veeraragavan et al. Genetic reduction of muscarinic M4 receptor modulates analgesic response and acoustic startle response in a mouse model of fragile X syndrome (FXS) Behav. Brain Res. 228 2012 1 8
81. S. Veeraragavan et al. Modulation of behavioral phenotypes by a muscarinic M1 antagonist in a mouse model of fragile X syndrome Psychopharmacology (Berl.) 217 2011 143 151
82. S. Veeraragavan et al. The modulation of fragile X behaviors by the muscarinic M4 antagonist, tropicamide Behav. Neurosci. 125 2011 783 790
83. S.S. Siller, and K. Broadie Matrix metalloproteinases and minocycline: therapeutic avenues for fragile X syndrome Neural. Plast. 2012 2012 124548
84. T. Bilousova et al. Minocycline promotes dendritic spine maturation and improves behavioral performance in the fragile X mouse model J. Med. Genet. 46 2009 94 102
85. S.E. Rotschafer et al. Minocycline treatment reverses ultrasonic vocalization production deficit in a mouse model of Fragile X syndrome Brain Res. 1439 2012 7 14
86. L.E. Dansie et al. Long-lasting effects of minocycline on behavior in young but not adult Fragile X mice Neuroscience 246 2013 186 198
87. S. Jacquemont et al. Epigenetic modification of the FMR1 Gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056 Sci. Transl. Med. 3 2011 64ra1
88. E.M. Berry-Kravis et al. Effects of STX209 (arbaclofen) on neurobehavioral function in children and adults with fragile X syndrome: a randomized, controlled, phase 2 trial Sci. Transl. Med. 4 2012 152ra127
89. M.J. Leigh et al. A randomized double-blind, placebo-controlled trial of minocycline in children and adolescents with fragile X syndrome J. Dev. Behav. Pediatr. 34 2013 147 155
90. D. Hessl et al. A solution to limitations of cognitive testing in children with intellectual disabilities: the case of fragile X syndrome J. Neurodev. Disord. 1 2009 33 45
91. E. Berry-Kravis et al. Outcome measures for clinical trials in fragile X syndrome J. Dev. Behav. Pediatr. 34 2013 508 522
92. R.J. Hagerman Physical and behavioral phenotype R.J. Hagerman, P.J. Hagerman, Fragile X syndrome: diagnosis, treatment and research 2002 Johns Hopkins University Press Baltimore, MA. 3 109
93. I. Heulens et al. Craniofacial characteristics of fragile X syndrome in mouse and man Eur J Hum Genet 21 8 2013 816 823
94. C.M. Spencer et al. Modifying behavioral phenotypes in Fmr1KO mice: genetic background differences reveal autistic-like responses Autism Res 4 1 2011 40 56
95. Z.H. Liu, and C.B. Smith Dissociation of social and nonsocial anxiety in a mouse model of fragile X syndrome Neurosci Lett 454 1 2009 62 66
96. S.A. Musumeci et al. Epilepsy and EEG findings in males with fragile X syndrome Epilepsia 40 8 1999 1092 1099
97. S.A. Musumeci et al. Audiogenic seizures susceptibility in transgenic mice with fragile X syndrome Epilepsia 41 2000 19 23
98. P.W. Frankland et al. Sensorimotor gating abnormalities in young males with fragile X syndrome and Fmr1-knockout mice Mol Psychiatry 9 4 2004 417 425
99. L. Chen, and M. Toth Fragile X mice develop sensory hyperreactivity to auditory stimuli Neuroscience 103 4 2001 1043 1050
100. D.M. Nielsen et al. Alterations in the auditory startle response in Fmr1 targeted mutant mouse models of fragile X syndrome Brain Res 927 1 2002 8 17
101. V.J. Hinton et al. Analysis of neocortex in three males with fragile X syndrome Am J Med Genet 41 3 1991 289 294