Structural basis for the rescue of hyperexcitable cells by the amyotrophic lateral sclerosis drug Riluzole.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 Sep 2024
28 Sep 2024
Historique:
received:
22
03
2024
accepted:
09
09
2024
medline:
29
9
2024
pubmed:
29
9
2024
entrez:
28
9
2024
Statut:
epublish
Résumé
Neuronal hyperexcitability is a key element of many neurodegenerative disorders including the motor neuron disease Amyotrophic Lateral Sclerosis (ALS), where it occurs associated with elevated late sodium current (I
Identifiants
pubmed: 39341837
doi: 10.1038/s41467-024-52539-4
pii: 10.1038/s41467-024-52539-4
doi:
Substances chimiques
Riluzole
7LJ087RS6F
Neuroprotective Agents
0
Voltage-Gated Sodium Channels
0
Sodium
9NEZ333N27
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8426Subventions
Organisme : Rosetrees Trust
ID : CF2-100001
Organisme : RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/V0183511
Organisme : RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/S017844
Organisme : RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/105581
Organisme : Diamond Light Source
ID : mutiple grants
Organisme : Wellcome Trust (Wellcome)
ID : studentship
Informations de copyright
© 2024. The Author(s).
Références
Lacomblez, L. et al. Long-term safety of riluzole in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Mot. Neuron Disord. Publ. World Fed. Neurol. Res. Group Mot. Neuron Dis. 3, 23–29 (2002).
van Es, M. A. et al. Amyotrophic lateral sclerosis. Lancet Lond. 390, 2084–2098 (2017).
doi: 10.1016/S0140-6736(17)31287-4
Brown, R. H. & Al-Chalabi, A. Amyotrophic lateral sclerosis. N. Engl. J. Med. 377, 1602 (2017).
pubmed: 29045202
doi: 10.1056/NEJMra1603471
Hinchcliffe, M. & Smith, A. Riluzole: real-world evidence supports significant extension of median survival times in patients with amyotrophic lateral sclerosis. Degener. Neurol. Neuromuscul. Dis. 7, 61–70 (2017).
pubmed: 30050378
pmcid: 6053101
Doble, A. The pharmacology and mechanism of action of riluzole. Neurology 47, S233–S241 (1996).
pubmed: 8959995
doi: 10.1212/WNL.47.6_Suppl_4.233S
Cheah, B. C. et al. Riluzole, neuroprotection and amyotrophic lateral sclerosis. Curr. Med. Chem. 17, 1942–1199 (2010).
pubmed: 20377511
doi: 10.2174/092986710791163939
Eisen, A. The dying forward hypothesis of ALS: tracing its history. Brain Sci. 11, 300 (2021).
pubmed: 33673524
pmcid: 7997258
doi: 10.3390/brainsci11030300
Bellingham, M. C. A review of the neural mechanisms of action and clinical efficiency of riluzole in treating amyotrophic lateral sclerosis: what have we learned in the last decade? CNS Neurosci. Ther. 17, 4–31 (2011).
pubmed: 20236142
pmcid: 6493865
doi: 10.1111/j.1755-5949.2009.00116.x
Benoit, E. & Escande, D. Riluzole specifically blocks inactivated Na channels in myelinated nerve fibre. Pflug. Arch. 419, 603–609 (1991).
doi: 10.1007/BF00370302
Hebert, T. et al. Block of the rat brain IIA sodium channel alpha subunit by the neuroprotective drug riluzole. Mol. Pharmacol. 45, 1055–1060 (1994).
pubmed: 8190096
Fouda, M. A. et al. Late sodium current: incomplete inactivation triggers seizures, myotonias, arrhythmias, and pain syndromes. J. Physiol. 600, 2835–2851 (2022).
pubmed: 35436004
doi: 10.1113/JP282768
Geevasinga, N. et al. Axonal ion channel dysfunction in c9orf72 familial amyotrophic lateral sclerosis. JAMA Neurol. 72, 49–57 (2015).
pubmed: 25384182
doi: 10.1001/jamaneurol.2014.2940
Vucic, S. & Kiernan, M. C. Novel threshold tracking techniques suggest that cortical hyperexcitability is an early feature of motor neuron disease. Brain 129, 2436–2446 (2006).
pubmed: 16835248
doi: 10.1093/brain/awl172
Vucic, S. & Kiernan, M. C. Upregulation of persistent sodium conductances in familial ALS. J. Neurol. Neurosurg. Psychiatry 81, 222–227 (2010).
pubmed: 19726402
doi: 10.1136/jnnp.2009.183079
Pieri, M. et al. Increased persistent sodium current determines cortical hyperexcitability in a genetic model of amyotrophic lateral sclerosis. Exp. Neurol. 215, 368–379 (2009).
pubmed: 19071115
doi: 10.1016/j.expneurol.2008.11.002
Kuo, J. et al. Increased persistent Na+ current and its effect on excitability in motoneurones cultured from mutant SOD1 mice. J. Physiol. 563, 843–854 (2005).
pubmed: 15649979
pmcid: 1665614
doi: 10.1113/jphysiol.2004.074138
Benedetti, L. et al. INaP selective inhibition reverts precocious inter- and motorneurons hyperexcitability in the Sod1-G93R zebrafish ALS model. Sci. Rep. 6, 24515 (2016).
pubmed: 27079797
pmcid: 4832213
doi: 10.1038/srep24515
Urbani, A. & Belluzzi, O. Riluzole inhibits the persistent sodium current in mammalian CNS neurons. Eur. J. Neurosci. 12, 3567–3574 (2000).
pubmed: 11029626
doi: 10.1046/j.1460-9568.2000.00242.x
Földi, M. C. et al. The mechanism of non-blocking inhibition of sodium channels revealed by conformation-selective photolabeling. Br. J. Pharmacol. 178, 1200–1217 (2021).
pubmed: 33450052
doi: 10.1111/bph.15365
Bagal, S. K. et al. Voltage gated sodium channels as drug discovery targets. Channels 9, 360–366 (2015).
pubmed: 26646477
pmcid: 4850042
doi: 10.1080/19336950.2015.1079674
Wisedchaisri, G. & Gamal El-Din, T. M. Druggability of voltage-gated sodium channels-exploring old and new drug receptor sites. Front. Pharmacol. 13, 858348 (2022).
pubmed: 35370700
pmcid: 8968173
doi: 10.3389/fphar.2022.858348
Alzheimer, C. et al. Modal gating of Na+ channels as a mechanism of persistent Na+ current in pyramidal neurons from rat and cat sensorimotor cortex. J. Neurosci. 13, 660–673 (1993).
pubmed: 8381170
pmcid: 6576639
doi: 10.1523/JNEUROSCI.13-02-00660.1993
Vilin, Y. Y. & Ruben, P. C. Slow inactivation in voltage-gated sodium channels: molecular substrates and contributions to channelopathies. Cell Biochem. Biophys. 35, 171–190 (2001).
pubmed: 11892790
doi: 10.1385/CBB:35:2:171
Groome, J. R. et al. Open- and closed-state fast inactivation in sodium channels. Channels 5, 65–78 (2011).
pubmed: 21099342
pmcid: 3052208
doi: 10.4161/chan.5.1.14031
ElBasiouny, S. M. et al. Persistent inward currents in spinal motoneurons: important for normal function but potentially harmful after spinal cord injury and in amyotrophic lateral sclerosis. Clin. Neurophysiol. Off. J. Int. Fed. Clin. Neurophysiol. 121, 1669–1679 (2010).
pubmed: 20462789
pmcid: 3000632
doi: 10.1016/j.clinph.2009.12.041
Makielski, J. C. Late sodium current: a mechanism for angina, heart failure, and arrhythmia. J. Cardiovasc. Pharmacol. 54, 279–286 (2009).
pmcid: 4454281
Yang, J. & Prescott, S. A. Homeostatic regulation of neuronal function: importance of degeneracy and pleiotropy. Front. Cell. Neurosci. 17, 1184563 (2023).
pubmed: 37333893
pmcid: 10272428
doi: 10.3389/fncel.2023.1184563
Aman, T. K. et al. Regulation of persistent Na current by interactions between β subunits of voltage-gated Na channels. J. Neurosci. 29, 2027–2042 (2009).
pubmed: 19228957
pmcid: 2667244
doi: 10.1523/JNEUROSCI.4531-08.2009
Yan, H. et al. Calmodulin limits pathogenic Na+ channel persistent current. J. Gen. Physiol. 149, 277–293 (2017).
pubmed: 28087622
pmcid: 5299624
doi: 10.1085/jgp.201611721
Ren, S. et al. Persistent sodium currents contribute to Aβ1-42-induced hyperexcitation of hippocampal CA1 pyramidal neurons. Neurosci. Lett. 580, 62–67 (2014).
pubmed: 25102326
doi: 10.1016/j.neulet.2014.07.050
Tidball, A. M. et al. Variant-specific changes in persistent or resurgent sodium current in SCN8A-related epilepsy patient-derived neurons. Brain J. Neurol. 143, 3025–3040 (2020).
doi: 10.1093/brain/awaa247
Munger, M. A. et al. Tetrodotoxin-sensitive neuronal-type Na+ channels: A novel and druggable target for prevention of atrial fibrillation. J. Am. Heart Assoc. 9, e015119 (2020).
pubmed: 32468902
pmcid: 7429002
doi: 10.1161/JAHA.119.015119
Desaphy, J.-F. et al. Preclinical evaluation of marketed sodium channel blockers in a rat model of myotonia discloses promising antimyotonic drugs. Exp. Neurol. 255, 96–102 (2014).
pubmed: 24613829
pmcid: 4004800
doi: 10.1016/j.expneurol.2014.02.023
Moon, E. S. et al. Riluzole attenuates neuropathic pain and enhances functional recovery in a rodent model of cervical spondylotic myelopathy. Neurobiol. Dis. 62, 394–406 (2014).
pubmed: 24184328
doi: 10.1016/j.nbd.2013.10.020
Bagnéris, C. et al. Prokaryotic NavMs channel as a structural and functional model for eukaryotic sodium channel antagonism. Proc. Natl Acad. Sci. (USA). 111, 8428–8433 (2014).
pubmed: 24850863
doi: 10.1073/pnas.1406855111
Sula, A. et al. The complete structure of an activated open sodium channel. Nat. Commun. 8, 14205 (2017).
pubmed: 28205548
pmcid: 5316852
doi: 10.1038/ncomms14205
Sula, A. et al. A tamoxifen receptor within a voltage-gated sodium channel. Mol. Cell 81, 1160–1169.e5 (2021).
pubmed: 33503406
pmcid: 7980221
doi: 10.1016/j.molcel.2020.12.048
Sait, L. G. et al. Cannabidiol interactions with voltage-gated sodium channels. eLife 9, e58593 (2020).
pubmed: 33089780
pmcid: 7641581
doi: 10.7554/eLife.58593
Choudhury, K. et al. An open state of a voltage-gated sodium channel involving a π-helix and conserved pore-facing asparagine. Biophys. J. 121, 11–22 (2022).
pubmed: 34890580
doi: 10.1016/j.bpj.2021.12.010
Payandeh, J. & Minor, D. L. Bacterial voltage-gated sodium channels (BacNaVs) from the soil, sea, and salt lakes enlighten molecular mechanisms of electrical signaling and pharmacology in the brain and heart. J. Mol. Biol. 427, 3–30 (2015).
pubmed: 25158094
doi: 10.1016/j.jmb.2014.08.010
Jayalakshmi, V. & Rama Krishna, N. CORCEMA refinement of the bound ligand conformation within the protein binding pocket in reversibly forming weak complexes using STD-NMR intensities. J. Magn. Reson. 168, 36–45 (2004).
pubmed: 15082247
doi: 10.1016/j.jmr.2004.01.017
Xiao, J. et al. Regulation and drug modulation of a voltage-gated sodium channel: Pivotal role of the S4-S5 linker in activation and slow inactivation. Proc. Natl Acad. Sci. (USA) 118, e2102285118 (2021).
pubmed: 34260401
doi: 10.1073/pnas.2102285118
Tao, E. & Corry, B. Characterizing fenestration size in sodium channel subtypes and their accessibility to inhibitors. Biophys. J. 121, 193–206 (2022).
pubmed: 34958776
doi: 10.1016/j.bpj.2021.12.025
Ragsdale, D. S. et al. Common molecular determinants of local anesthetic, antiarrhythmic, and anticonvulsant block of voltage-gated Na+ channels. Proc. Natl Acad. Sci. (USA) 93, 9270–9275 (1996).
pubmed: 8799190
pmcid: 38631
doi: 10.1073/pnas.93.17.9270
Bai, C.-X. et al. Involvement of local anesthetic binding sites on IVS6 of sodium channels in fast and slow inactivation. Neurosci. Lett. 337, 41–45 (2003).
pubmed: 12524167
doi: 10.1016/S0304-3940(02)01288-0
Chatterjee, S. et al. The voltage-gated sodium channel pore exhibits conformational flexibility during slow inactivation. J. Gen. Physiol. 150, 1333–1347 (2018).
pubmed: 30082431
pmcid: 6122925
doi: 10.1085/jgp.201812118
Song, J.-H. et al. Differential action of riluzole on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels. J. Pharmacol. Exp. Ther. 282, 707–714 (1997).
pubmed: 9262334
Huang, J. et al. Dual-pocket inhibition of Nav channels by the antiepileptic drug lamotrigine. Proc. Natl Acad. Sci. (USA) 120, e2309773120 (2023).
pubmed: 37782796
doi: 10.1073/pnas.2309773120
Pan, X. et al. Structure of the human voltage-gated sodium channel Nav1.4 in complex with β1. Science 362, eaau2486 (2018).
pubmed: 30190309
doi: 10.1126/science.aau2486
Cannon, S. C. Sodium channelopathies of skeletal muscle. Handb. Exp. Pharmacol. 246, 309–330 (2018).
pubmed: 28939973
pmcid: 5866235
doi: 10.1007/164_2017_52
Webb, J. & Cannon, S. C. Cold-induced defects of sodium channel gating in atypical periodic paralysis plus myotonia. Neurology 70, 755–761 (2008).
pubmed: 17898326
doi: 10.1212/01.wnl.0000265397.70057.d8
Ghovanloo, M.-R. et al. A mixed periodic paralysis & myotonia mutant P1158S imparts pH-sensitivity in skeletal muscle voltage-gated sodium channels. Sci. Rep. 8, 6304 (2018).
pubmed: 29674667
pmcid: 5908869
doi: 10.1038/s41598-018-24719-y
Hille, B. Local anesthetics: hydrophilic and hydrophobic pathways for the drug- receptor reaction. J. Gen. Physiol. 69, 497–515 (1977).
pubmed: 300786
doi: 10.1085/jgp.69.4.497
Gamal El-Din, T.-M. et al. Fenestrations control resting-state block of a voltage-gated sodium channel. Proc. Natl Acad. Sci. USA 115, 13111–13116 (2018).
pubmed: 30518562
pmcid: 6304959
doi: 10.1073/pnas.1814928115
Li, T. et al. Structural Basis for the Modulation of Human KCNQ4 by Small-Molecule Drugs. Mol. Cell 81, 25–37.e4 (2021).
pubmed: 33238160
doi: 10.1016/j.molcel.2020.10.037
Zhao, Y. et al. Molecular basis for ligand modulation of a mammalian voltage-gated Ca2+ channel. Cell 177, 1495–1506.e12 (2019).
pubmed: 31150622
doi: 10.1016/j.cell.2019.04.043
Payandeh, J. & Volgraf, M. Ligand binding at the protein–lipid interface: strategic considerations for drug design. Nat. Rev. Drug Discov. 20, 710–722 (2021).
pubmed: 34257432
doi: 10.1038/s41573-021-00240-2
Vauquelin, G. On the ‘micro’-pharmacodynamic and pharmacokinetic mechanisms that contribute to long-lasting drug action. Expert Opin. Drug Discov. 10, 1085–1098 (2015).
pubmed: 26165720
doi: 10.1517/17460441.2015.1067196
Green, M. R., Sambrook, J. & Sambrook, J. Molecular Cloning: A Laboratory Manual. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y, 2012).
Winter, G. xia2: an expert system for macromolecular crystallography data reduction. J. Appl. Crystallogr. 43, 186–190 (2010).
doi: 10.1107/S0021889809045701
Waterman, D. G. et al. Diffraction-geometry refinement in the DIALS framework. Acta Crystallogr. Sect. Struct. Biol. 72, 558–575 (2016).
doi: 10.1107/S2059798316002187
Evans, P. R. & Murshudov, G. N. How good are my data and what is the resolution? Acta Crystallogr. D. Biol. Crystallogr. 69, 1204–1214 (2013).
pubmed: 23793146
pmcid: 3689523
doi: 10.1107/S0907444913000061
McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658–674 (2007).
pubmed: 19461840
pmcid: 2483472
doi: 10.1107/S0021889807021206
Emsley, P. et al. Features and development of Coot. Acta Crystallogr. D. Biol. Crystallogr. 66, 486–501 (2010).
pubmed: 20383002
pmcid: 2852313
doi: 10.1107/S0907444910007493
Murshudov, G. N. et al. REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr. D. Biol. Crystallogr. 67, 355–367 (2011).
pubmed: 21460454
pmcid: 3069751
doi: 10.1107/S0907444911001314
Bricogne G. et al. BUSTER version 2.10.4. Cambridge, United Kingdom: Global Phasing Ltd, (2017).
PyMOL | pymol.org. https://pymol.org/2/ .
Wagner, A. et al. In-vacuum long-wavelength macromolecular crystallography. Acta Crystallogr. Sect. Struct. Biol. 72, 430–439 (2016).
doi: 10.1107/S2059798316001078
Thorn, A. & Sheldrick, G. M. ANODE: anomalous and heavy-atom density calculation. J. Appl. Crystallogr. 44, 1285–1287 (2011).
pubmed: 22477786
pmcid: 3246834
doi: 10.1107/S0021889811041768
Abdelsayed, M. et al. Differential thermosensitivity in mixed syndrome cardiac sodium channel mutants. J. Physiol. 593, 4201–4223 (2015).
pubmed: 26131924
pmcid: 4594293
doi: 10.1113/JP270139
Abdelsayed, M. et al. The efficacy of Ranolazine on E1784K is altered by temperature and calcium. Sci. Rep. 8, 3643 (2018).
pubmed: 29483621
pmcid: 5827758
doi: 10.1038/s41598-018-22033-1
Wu, E. L. et al. CHARMM-GUI membrane builder toward realistic biological membrane simulations. J. Comput. Chem. 35, 1997–2004 (2014).
pubmed: 25130509
pmcid: 4165794
doi: 10.1002/jcc.23702
Jo, S. et al. CHARMM-GUI Membrane builder for mixed bilayers and its application to yeast membranes. Biophys. J. 97, 50–58 (2009).
pubmed: 19580743
pmcid: 2711372
doi: 10.1016/j.bpj.2009.04.013
Jo, S. et al. Automated builder and database of protein/embrane complexes for molecular dynamics simulations. PLOS ONE 2, e880 (2007).
pubmed: 17849009
pmcid: 1963319
doi: 10.1371/journal.pone.0000880
Lee, J. et al. CHARMM-GUI Membrane builder for complex biological membrane simulations with glycolipids and lipoglycans. J. Chem. Theory & Comput. 15, 775–786 (2019).
Jo, S. et al. CHARMM-GUI: a web-based graphical user interface for CHARMM. J. Comput. Chem. 29, 1859–1865 (2008).
pubmed: 18351591
doi: 10.1002/jcc.20945
Vanommeslaeghe, K. et al. CHARMM general force field: a force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J. Comput. Chem. 31, 671–690 (2010).
pubmed: 19575467
pmcid: 2888302
doi: 10.1002/jcc.21367
Kim, S. et al. CHARMM-GUI ligand reader and modeler for CHARMM force field generation of small molecules. J. Comput. Chem. 38, 1879–1886 (2017).
pubmed: 28497616
pmcid: 5488718
doi: 10.1002/jcc.24829
Abraham, M. J. et al. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1–2, 19–25 (2015).
doi: 10.1016/j.softx.2015.06.001
Huang, J. et al. CHARMM36m: an improved force field for folded and intrinsically disordered proteins. Nat. Methods 14, 71–73 (2017).
pubmed: 27819658
doi: 10.1038/nmeth.4067
Hess, B. et. al., LINCS: A linear constraint solver for molecular simulations. J. Comput. Chem. 18, 1463–1472 (1997).
doi: 10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H
Evans, D. J. & Holian, B. L. The Nose–Hoover thermostat. J. Chem. Phys. 83, 4069–4074 (1985).
doi: 10.1063/1.449071
Parrinello, M. & Rahman, A. Polymorphic transitions in single crystals: a new molecular dynamics method. J. Appl. Phys. 52, 7182–7190 (1981).
doi: 10.1063/1.328693
Daura, X. et al. Peptide folding: when simulation meets experiment. Angew. Chem. Int. Ed. 38, 236–240 (1999).
doi: 10.1002/(SICI)1521-3773(19990115)38:1/2<236::AID-ANIE236>3.0.CO;2-M
Michaud-Agrawal, N., Denning, E. J., Woolf, T. B. & Beckstein, O. MDAnalysis: a toolkit for the analysis of molecular dynamics simulations. J. Comput. Chem. 32, 2319–2327 (2011).
pubmed: 21500218
pmcid: 3144279
doi: 10.1002/jcc.21787
Gowers, R. et al. MDAnalysis: a python package for the rapid analysis of molecular dynamics simulations. 98–105 (Austin, Texas, 2016). https://doi.org/10.25080/Majora-629e541a-00e .