Therapeutic efficacy of the BKCa channel opener chlorzoxazone in a mouse model of Fragile X syndrome

Pieretti M, Zhang FP, Fu YH, Warren ST, Oostra BA, Caskey CT, et al. Absence of expression of the FMR-1 gene in fragile X syndrome. Cell. 1991;66:817–22.

Article  CAS  PubMed  Google Scholar 

Santoro MR, Bray SM, Warren ST. Molecular mechanisms of fragile X syndrome: a twenty-year perspective. Annu Rev Pathol. 2012;7:219–45.

Article  CAS  PubMed  Google Scholar 

Greenough WT, Klintsova AY, Irwin SA, Galvez R, Bates KE, Weiler IJ. Synaptic regulation of protein synthesis and the fragile X protein. Proc Natl Acad Sci USA. 2001;98:7101–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tranfaglia MR. The psychiatric presentation of fragile X: evolution of the diagnosis and treatment of the psychiatric comorbidities of fragile X syndrome. Dev Neurosci. 2011;33:337–48.

Article  CAS  PubMed  Google Scholar 

Aishworiya R, Valica T, Hagerman R, Restrepo B. An update on psychopharmacological treatment of autism spectrum disorder. Neurotherapeutics. 2022;19:248–62. https://doi.org/10.1007/s13311-022-01183-1

Article  CAS  PubMed  PubMed Central  Google Scholar 

Johnson D, Clark C, Hagerman R. Targeted treatments for fragile X syndrome. Adv Neurobiol. 2023;30:225–53. https://doi.org/10.1007/978-3-031-21054-9_10

Article  PubMed  Google Scholar 

Protic D, Salcedo-Arellano MJ, Dy JB, Potter LA, Hagerman RJ. New targeted treatments for fragile X syndrome. Curr Pediatr Rev. 2019;15:251–8. https://doi.org/10.2174/1573396315666190625110748

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang LW, Berry-Kravis E, Hagerman RJ. Fragile X: leading the way for targeted treatments in autism. Neurotherapeutics. 2010;7:264–74.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wen TH, Binder DK, Ethell IM, Razak KA. The perineuronal ‘safety’ net? Perineuronal net abnormalities in neurological disorders. Front Mol Neurosci. 2018;11:270 https://doi.org/10.3389/fnmol.2018.00270

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gantois I, Khoutorsky A, Popic J, Aguilar-Valles A, Freemantle E, Cao R, et al. Metformin ameliorates core deficits in a mouse model of fragile X syndrome. Nat Med. 2017;23:674–7. https://doi.org/10.1038/nm.4335

Article  CAS  PubMed  Google Scholar 

Gkogkas CG, Khoutorsky A, Cao R, Jafarnejad SM, Prager-Khoutorsky M, Giannakas N, et al. Pharmacogenetic inhibition of eIF4E-dependent Mmp9 mRNA translation reverses fragile X syndrome-like phenotypes. Cell Rep. 2014;9:1742–55. https://doi.org/10.1016/j.celrep.2014.10.064

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cogram P, Deacon RMJ, Warner-Schmidt JL, von Schimmelmann MJ, Abrahams BS, During MJ. Gaboxadol normalizes behavioral abnormalities in a mouse model of fragile X syndrome. Front Behav Neurosci. 2019;13:141. https://doi.org/10.3389/fnbeh.2019.00141

Article  CAS  PubMed  PubMed Central  Google Scholar 

Olmos-Serrano JL, Corbin JG, Burns MP. The GABA(A) receptor agonist THIP ameliorates specific behavioral deficits in the mouse model of fragile X syndrome. Dev Neurosci. 2011;33:395–403.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wafford KA, Ebert B. Gaboxadol-a new awakening in sleep. Curr Opin Pharm. 2006;6:30–6. https://doi.org/10.1016/j.coph.2005.10.004

Article  CAS  Google Scholar 

Bartholini G. GABA receptor agonists: pharmacological spectrum and therapeutic actions. Med Res Rev. 1985;5:55–75. https://doi.org/10.1002/med.2610050103

Article  CAS  PubMed  Google Scholar 

N’Gouemo P. BKCa channel dysfunction in neurological diseases. Front Physiol. 2014;5:373. https://doi.org/10.3389/fphys.2014.00373

Article  PubMed  PubMed Central  Google Scholar 

Kshatri AS, Gonzalez-Hernandez A, Giraldez T. Physiological roles and therapeutic potential of Ca(2+) activated potassium channels in the nervous system. Front Mol Neurosci. 2018;11:258. https://doi.org/10.3389/fnmol.2018.00258

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ancaten-Gonzalez C, Segura I, Alvarado-Sanchez R, Chavez AE, Latorre R. Ca(2+)- and voltage-activated K(+) (BK) channels in the nervous system: one gene, a myriad of physiological functions. Int J Mol Sci. 2023;24. https://doi.org/10.3390/ijms24043407

Orfali R, Albanyan N. Ca(2+)-sensitive potassium channels. Molecules. 2023;28. https://doi.org/10.3390/molecules28020885

Echeverria F, Gonzalez-Sanabria N, Alvarado-Sanchez R, Fernandez M, Castillo K, Latorre R. Large conductance voltage-and calcium-activated K(+) (BK) channel in health and disease. Front Pharm. 2024;15:1373507 https://doi.org/10.3389/fphar.2024.1373507

Article  CAS  Google Scholar 

Deng PY, Klyachko VA. Genetic upregulation of BK channel activity normalizes multiple synaptic and circuit defects in a mouse model of fragile X syndrome. J Physiol. 2016;594:83–97. https://doi.org/10.1113/JP271031

Article  CAS  PubMed  Google Scholar 

Deng PY, Rotman Z, Blundon JA, Cho Y, Cui J, Cavalli V, et al. FMRP regulates neurotransmitter release and synaptic information transmission by modulating action potential duration via BK channels. Neuron. 2013;77:696–711. https://doi.org/10.1016/j.neuron.2012.12.018

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kshatri A, Cerrada A, Gimeno R, Bartolome-Martin D, Rojas P, Giraldez T. Differential regulation of BK channels by fragile X mental retardation protein. J Gen Physiol. 2020;152. https://doi.org/10.1085/jgp.201912502

Hebert B, Pietropaolo S, Meme S, Laudier B, Laugeray A, Doisne N, et al. Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by a BKCa channel opener molecule. Orphanet J Rare Dis. 2014;9:124.

Article  PubMed  PubMed Central  Google Scholar 

Zhang Y, Bonnan A, Bony G, Ferezou I, Pietropaolo S, Ginger M, et al. Dendritic channelopathies contribute to neocortical and sensory hyperexcitability in Fmr1(-/y) mice. Nat Neurosci. 2014;17:1701–9. https://doi.org/10.1038/nn.3864

Article  CAS  PubMed  Google Scholar 

Myrick LK, Deng PY, Hashimoto H, Oh YM, Cho Y, Poidevin MJ, et al. Independent role for presynaptic FMRP revealed by an FMR1 missense mutation associated with intellectual disability and seizures. Proc Natl Acad Sci USA. 2015;112:949–56. https://doi.org/10.1073/pnas.1423094112

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang ZW. Regulation of synaptic transmission by presynaptic CaMKII and BK channels. Mol Neurobiol. 2008;38:153–66. https://doi.org/10.1007/s12035-008-8039-7

Article  CAS  PubMed  PubMed Central  Google Scholar 

van Welie I, du Lac S. Bidirectional control of BK channel open probability by CAMKII and PKC in medial vestibular nucleus neurons. J Neurophysiol. 2011;105:1651–9. https://doi.org/10.1152/jn.00058.2011

Article  CAS  PubMed  PubMed Central  Google Scholar 

Darnell JC, Van Driesche SJ, Zhang C, Hung KY, Mele A, Fraser CE, et al. FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell. 2011;146:247–61. https://doi.org/10.1016/j.cell.2011.06.013

Article  CAS  PubMed  PubMed Central  Google Scholar 

Comments (0)

No login
gif