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2000
Volume 24, Issue 8
  • ISSN: 1871-5273
  • E-ISSN: 1996-3181

Abstract

Sodium channels are necessary for electrical activity in modules of the nervous system. When such channels fail to work properly, it may cause different neurological diseases. This review will discuss how particular mutation in these channels leads to different diseases. Positive alterations can lead to such diseases as epilepsy, or any muscle disorder due to over activation of neurons. Conversely, loss-of-function mutations may cause heart diseases and problems regarding motor and mental activity since neurons are not functioning well because of lost machinery. The review would discuss over familiar channelopathies such as genetic epilepsies, the familial hemiplegic migraine, and Para myotonia congenital and relatively new interrelations with the complex ailments including Alzheimer’s, Parkinson’s and multiple sclerosis. Thus, knowledge of these mechanisms is important in designing specific therapeutic approaches. There is a rationale for altering the sodium channel activity in the treatment of these neurological disorders by drugs or indeed genetic methods. Thus, the review is undertaken to provide clear distinctions and discuss the issues related to sodium channel mutations for the potential development of individualized medicine. The review also gives information on the function and general distribution of voltage-gated sodium channels (VGSCs), how their activity is controlled, and what their structure is like. The purpose therefore is to draw understanding over the apparently multifaceted functions exerted by VGSCs in the nervous system relative to several diseases. This knowledge is imperative in the attempt to produce treatments for these disabling disorders.

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References

  1. FeiginV.L. NicholsE. AlamT. Global, regional, and national burden of neurological disorders, 1990-2016: A systematic analysis for the global burden of disease study 2016.Lancet Neurol.201918545948010.1016/S1474‑4422(18)30499‑X 30879893
     [Google Scholar]
  2. BarbieriR. NizzariM. ZanardiI. PuschM. GavazzoP. Voltage-gated sodium channel dysfunctions in neurological disorders.Life2023135119110.3390/life13051191 37240836
     [Google Scholar]
  3. BouzaA.A. IsomL.L. Voltage-gated sodium channel β subunits and their related diseases.Handb. Exp. Pharmacol.2018246423450
     [Google Scholar]
  4. MakauC.M. TowettP.K. KanuiT.I. AbelsonK.S.P. Effects of inhibition of Nav1.3, Nav1.7, and Nav1.8 channels on pain‐related behavior in Speke’s hinge‐back tortoise (Kinixys spekii).J. Neurosci. Res.20241021e2527410.1002/jnr.25274 38284848
     [Google Scholar]
  5. WangJ. OuS.W. WangY.J. Distribution and function of voltage-gated sodium channels in the nervous system.Channels (Austin)201711653455410.1080/19336950.2017.1380758 28922053
     [Google Scholar]
  6. KimJ.B. Channelopathies.Korean J. Pediatr.201457111810.3345/kjp.2014.57.1.1 24578711
     [Google Scholar]
  7. WisedchaisriG. Gamal El-DinT.M. Druggability of voltage-gated sodium channels—exploring old and new drug receptor sites.Front. Pharmacol.20221385834810.3389/fphar.2022.858348 35370700
     [Google Scholar]
  8. BagalS.K. MarronB.E. OwenR.M. StorerR.I. SwainN.A. Voltage gated sodium channels as drug discovery targets.Channels20159636036610.1080/19336950.2015.1079674 26646477
     [Google Scholar]
  9. MoreauA. ChahineM. A new cardiac channelopathy: From clinical phenotypes to molecular mechanisms associated with Nav1. 5 gating pores.Front. Cardiovasc. Med.2018513910.3389/fcvm.2018.00139 30356750
     [Google Scholar]
  10. PereiraA.R.S. Effect of seizures on the cognitive and behavioral phenotypes of mouse models carrying the Scn1a gene mutation: Implications for Dravet Syndrome.Université Côte d'Azur2017
     [Google Scholar]
  11. CazzatoD. Clinical and genetic characterization of neuropathic pain through the model of small fiber neuropathy: Implication for diabetic neuropathy.Doctoral Thesis SFERA Archive of Research Products of the University of Ferrara2020
     [Google Scholar]
  12. PatelR. DickensonA.H. Neuropharmacological basis for multimodal analgesia in chronic pain.Postgrad. Med.2022134324525910.1080/00325481.2021.1985351 34636261
     [Google Scholar]
  13. PalanisamyC.P. PeiJ. AlugojuP. New strategies of neurodegenerative disease treatment with extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs).Theranostics202313124138416510.7150/thno.83066 37554286
     [Google Scholar]
  14. ZhangA.H. SharmaG. UndheimE.A.B. JiaX. MobliM. A complicated complex: Ion channels, voltage sensing, cell membranes and peptide inhibitors.Neurosci. Lett.2018679354710.1016/j.neulet.2018.04.030 29684532
     [Google Scholar]
  15. BianY. TuoJ. HeL. Voltage-gated sodium channels in cancer and their specific inhibitors.Pathol. Res. Pract.202325115490910.1016/j.prp.2023.154909 37939447
     [Google Scholar]
  16. MendesL.C. VianaG.M.M. NencioniA.L.A. PimentaD.C. NetoB.E. Scorpion peptides and ion channels: An insightful review of mechanisms and drug development.Toxins202315423810.3390/toxins15040238 37104176
     [Google Scholar]
  17. MantegazzaM. CatterallW.A. Voltage-Gated Na+ Channels.4th Ed.New YorkJasper's Basic Mechanisms of the Epilepsies201210.1093/med/9780199746545.003.0004
     [Google Scholar]
  18. XuL. DingX. WangT. MouS. SunH. HouT. Voltage-gated sodium channels: Structures, functions, and molecular modeling.Drug Discov. Today20192471389139710.1016/j.drudis.2019.05.014 31129313
     [Google Scholar]
  19. MercierA. BoisP. ChatelierA. Sodium channel trafficking.Handb. Exp. Pharmacol.2018246125145
     [Google Scholar]
  20. O’MalleyH.A. IsomL.L. Sodium channel β subunits: Emerging targets in channelopathies.Annu. Rev. Physiol.201577148150410.1146/annurev‑physiol‑021014‑071846 25668026
     [Google Scholar]
  21. MeislerM.H. HillS.F. YuW. Sodium channelopathies in neurodevelopmental disorders.Nat. Rev. Neurosci.202122315216610.1038/s41583‑020‑00418‑4 33531663
     [Google Scholar]
  22. YamakawaK. Mutations of voltage-gated sodium channel genes SCN1A and SCN2A in epilepsy, intellectual disability, and autism.Elsevier: Neuronal and synaptic dysfunction in autism Spectrum disorder and intellectual disability.20162335110.1016/B978‑0‑12‑800109‑7.00015‑7
     [Google Scholar]
  23. TurnerT.J. ZourrayC. SchorgeS. LignaniG. Recent advances in gene therapy for neurodevelopmental disorders with epilepsy.J. Neurochem.2021157222926210.1111/jnc.15168 32880951
     [Google Scholar]
  24. HelbigK.L. GoldbergE.M. SCN3A-related neurodevelopmental disorder.University of Washington, Seattle: Seattle (WA)202119932024
     [Google Scholar]
  25. ZamanT. HelbigK.L. ClatotJ. SCN3A‐related neurodevelopmental disorder: A spectrum of epilepsy and brain malformation.Ann. Neurol.202088234836210.1002/ana.25809 32515017
     [Google Scholar]
  26. TuckerG.J. Seizure disorders presenting with psychiatric symptomatology.Psychiatr. Clin. North Am.1998213625635, vi10.1016/S0193‑953X(05)70027‑79774800
     [Google Scholar]
  27. EncinasA.C. WatkinsJ.C. LongoriaI.A. JohnsonJ.P.Jr HammerM.F. Variable patterns of mutation density among NaV1.1, NaV1.2 and NaV1.6 point to channel-specific functional differences associated with childhood epilepsy.PLoS One2020158e023812110.1371/journal.pone.0238121 32845893
     [Google Scholar]
  28. DravetC. Dravet syndrome history.Dev. Med. Child Neurol.201153s2Suppl. 21610.1111/j.1469‑8749.2011.03964.x 21504424
     [Google Scholar]
  29. OgiwaraI. MiyamotoH. MoritaN. 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.200727225903591410.1523/JNEUROSCI.5270‑06.2007 17537961
     [Google Scholar]
  30. AuffenbergE. HedrichU.B.S. BarbieriR. Hyperexcitable interneurons trigger cortical spreading depression in an Scn1a migraine model.J. Clin. Invest.202113121e14220210.1172/JCI142202 34546973
     [Google Scholar]
  31. SpampanatoJ. EscaygA. MeislerM.H. GoldinA.L. Functional effects of two voltage-gated sodium channel mutations that cause generalized epilepsy with febrile seizures plus type 2.J. Neurosci.200121197481749010.1523/JNEUROSCI.21‑19‑07481.2001 11567038
     [Google Scholar]
  32. LossinC. RhodesT.H. DesaiR.R. Epilepsy-associated dysfunction in the voltage-gated neuronal sodium channel SCN1A.J. Neurosci.20032336112891129510.1523/JNEUROSCI.23‑36‑11289.2003 14672992
     [Google Scholar]
  33. TangB. DuttK. PapaleL. A BAC transgenic mouse model reveals neuron subtype-specific effects of a Generalized Epilepsy with Febrile Seizures Plus (GEFS+) mutation.Neurobiol. Dis.20093519110210.1016/j.nbd.2009.04.007 19409490
     [Google Scholar]
  34. CheahC.S. YuF.H. WestenbroekR.E. Specific deletion of Na V 1.1 sodium channels in inhibitory interneurons causes seizures and premature death in a mouse model of Dravet syndrome.Proc. Natl. Acad. Sci. USA201210936146461465110.1073/pnas.1211591109 22908258
     [Google Scholar]
  35. PietrobonD. MoskowitzM.A. Pathophysiology of Migraine.Annu. Rev. Physiol.201375136539110.1146/annurev‑physiol‑030212‑183717 23190076
     [Google Scholar]
  36. DichgansM. FreilingerT. EcksteinG. Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine.Lancet2005366948337137710.1016/S0140‑6736(05)66786‑4 16054936
     [Google Scholar]
  37. VanmolkotKRJ BabiniE VriesdB The novel p.L1649Q mutation in the SCN1A epilepsy gene is associated with familial hemiplegic migraine: Genetic and functional studies.Hum. Mutat.2007285522210.1002/humu.9486 17397047
     [Google Scholar]
  38. BertelliS. BarbieriR. PuschM. GavazzoP. Gain of function of sporadic/familial hemiplegic migraine-causing SCN1A mutations: Use of an optimized cDNA.Cephalalgia201939447748810.1177/0333102418788336 29986598
     [Google Scholar]
  39. BarbieriR. BertelliS. PuschM. GavazzoP. Late sodium current blocker GS967 inhibits persistent currents induced by familial hemiplegic migraine type 3 mutations of the SCN1A gene.J. Headache Pain201920110710.1186/s10194‑019‑1056‑2 31730442
     [Google Scholar]
  40. CestèleS. ScalmaniP. RusconiR. TerragniB. FranceschettiS. MantegazzaM. Self-limited hyperexcitability: Functional effect of a familial hemiplegic migraine mutation of the Nav1.1 (SCN1A) Na+ channel.J. Neurosci.200828297273728310.1523/JNEUROSCI.4453‑07.2008 18632931
     [Google Scholar]
  41. ReynoldsC. KingM.D. GormanK.M. The phenotypic spectrum of SCN2A-related epilepsy.Eur. J. Paediatr. Neurol.20202411712210.1016/j.ejpn.2019.12.016 31924505
     [Google Scholar]
  42. ArdlieK.G. DelucaD.S. SegrèA.V. The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans.Science2015348623564866010.1126/science.1262110 25954001
     [Google Scholar]
  43. RauchA. WieczorekD. GrafE. Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: An exome sequencing study.Lancet201238098541674168210.1016/S0140‑6736(12)61480‑9 23020937
     [Google Scholar]
  44. SandersS.J. CampbellA.J. CottrellJ.R. Progress in understanding and treating SCN2A-mediated disorders.Trends Neurosci.201841744245610.1016/j.tins.2018.03.011 29691040
     [Google Scholar]
  45. CooperE.D.M. HawkinsN.A. MisraS.N. Cellular and behavioral effects of altered NaV1.2 sodium channel ion permeability in Scn2a K1422E mice.Hum. Mol. Genet.202231172964298810.1093/hmg/ddac087 35417922
     [Google Scholar]
  46. PeruccaP. PeruccaE. Identifying mutations in epilepsy genes: Impact on treatment selection.Epilepsy Res.2019152183010.1016/j.eplepsyres.2019.03.001 30870728
     [Google Scholar]
  47. HollandK.D. KearneyJ.A. GlauserT.A. Mutation of sodium channel SCN3A in a patient with cryptogenic pediatric partial epilepsy.Neurosci. Lett.20084331657010.1016/j.neulet.2007.12.064 18242854
     [Google Scholar]
  48. EstacionM. GasserA. HajjD.S.D. WaxmanS.G. A sodium channel mutation linked to epilepsy increases ramp and persistent current of Nav1.3 and induces hyperexcitability in hippocampal neurons.Exp. Neurol.2010224236236810.1016/j.expneurol.2010.04.012 20420834
     [Google Scholar]
  49. JohannesenK.M. GardellaE. EncinasA.C. The spectrum of intermediateSCN 8A ‐related epilepsy.Epilepsia201960583084410.1111/epi.14705 30968951
     [Google Scholar]
  50. HammerM.F. XiaM. SchreiberJ.M. SCN8A-related epilepsy and/or neurodevelopmental disorders.University of WashingtonSeattleGeneReviews Seattle (WA):2023[https://www.ncbi.nlm.nih.gov/books/NBK379665/
    [Google Scholar]
  51. VeeramahK.R. O’BrienJ.E. MeislerM.H. De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEP.Am. J. Hum. Genet.201290350251010.1016/j.ajhg.2012.01.006 22365152
     [Google Scholar]
  52. LansdonP.A. Bidirectional communication between the brain and gut microbiota in Shudderer, a Drosophila Nav channel mutant.University of Iowa: Doctoral Dissertation201810.17077/etd.5l60‑x98x
     [Google Scholar]
  53. FaustinoD. BrinkmeierH. LogothetiS. Novel integrated workflow allows production and in-depth quality assessment of multifactorial reprogrammed skeletal muscle cells from human stem cells.Cell. Mol. Life Sci.202279522910.1007/s00018‑022‑04264‑8 35396689
     [Google Scholar]
  54. TalwarD. HammerM.F. SCN8A epilepsy, developmental encephalopathy, and related disorders.Pediatr. Neurol.2021122768310.1016/j.pediatrneurol.2021.06.011 34353676
     [Google Scholar]
  55. HebbarM. TaweelA.N. GillI. Expanding the genotype-phenotype spectrum in SCN8A-related disorders.BMC Neurol.20242413110.1186/s12883‑023‑03478‑y 38233770
     [Google Scholar]
  56. DormerA. NarayananM. SchentagJ. A review of the therapeutic targeting of SCN9A and Nav1. 7 for pain relief in current human clinical trials.J. Pain Res.2023161487149810.2147/JPR.S388896 37168847
     [Google Scholar]
  57. DrenthJ.P.H. WaxmanS.G. Mutations in sodium-channel gene SCN9A cause a spectrum of human genetic pain disorders.J. Clin. Invest.2007117123603360910.1172/JCI33297 18060017
     [Google Scholar]
  58. GardellaE. MøllerR.S. Phenotypic and genetic spectrum ofSCN 8A ‐related disorders, treatment options, and outcomes.Epilepsia201960S3Suppl. 3S77S8510.1111/epi.16319 31904124
     [Google Scholar]
  59. SchefferI.E. NabboutR. SCN1A‐related phenotypes: Epilepsy and beyond.Epilepsia201960S3Suppl. 3S17S2410.1111/epi.16386 31904117
     [Google Scholar]
  60. BrunklausA. LalD. Sodium channel epilepsies and neurodevelopmental disorders: From disease mechanisms to clinical application.Dev. Med. Child Neurol.202062778479210.1111/dmcn.14519 32227486
     [Google Scholar]
  61. BakerM.D. NassarM.A. Painful and painless mutations of SCN9A and SCN11A voltage-gated sodium channels.Pflugers Arch.2020472786588010.1007/s00424‑020‑02419‑9 32601768
     [Google Scholar]
  62. GinanneschiF. RubegniA. MoroF. VolpiN. SantorelliF.M. RossiA. SCN11A variant as possible pain generator in sensory axonal neuropathy.Neurol. Sci.20194061295129710.1007/s10072‑019‑3703‑4 30623267
     [Google Scholar]
  63. SelkoeD.J. Deciphering the genesis and fate of amyloid β-protein yields novel therapies for Alzheimer disease.J. Clin. Invest.2002110101375138110.1172/JCI0216783 12438432
     [Google Scholar]
  64. ZhangY. ThompsonR. ZhangH. XuH. APP processing in Alzheimer’s disease.Mol. Brain201141310.1186/1756‑6606‑4‑3 21214928
     [Google Scholar]
  65. LiuC. TanF.C.K. XiaoZ.C. DaweG.S. Amyloid precursor protein enhances Nav1.6 sodium channel cell surface expression.J. Biol. Chem.201529019120481205710.1074/jbc.M114.617092 25767117
     [Google Scholar]
  66. LiS. WangX. MaQ.H. Amyloid precursor protein modulates Nav1.6 sodium channel currents through a Go-coupled JNK pathway.Sci. Rep.2016613932010.1038/srep39320 28008944
     [Google Scholar]
  67. CicconeR. FrancoC. PiccialliI. Amyloid β-induced upregulation of Nav1. 6 underlies neuronal hyperactivity in Tg2576 Alzheimer’s disease mouse model.Sci. Rep.2019911359210.1038/s41598‑019‑50018‑1 31537873
     [Google Scholar]
  68. VassarR. KovacsD.M. YanR. WongP.C. The β-secretase enzyme BACE in health and Alzheimer’s disease: Regulation, cell biology, function, and therapeutic potential.J. Neurosci.20092941127871279410.1523/JNEUROSCI.3657‑09.2009 19828790
     [Google Scholar]
  69. KimD.Y. GersbacherM.T. InquimbertP. KovacsD.M. Reduced sodium channel Na(v)1.1 levels in BACE1-null mice.J. Biol. Chem.2011286108106811610.1074/jbc.M110.134692 21190943
     [Google Scholar]
  70. HammondC. BergmanH. BrownP. Pathological synchronization in Parkinson’s disease: Networks, models and treatments.Trends Neurosci.200730735736410.1016/j.tins.2007.05.004 17532060
     [Google Scholar]
  71. DolgachevaL.P. ZinchenkoV.P. GoncharovN.V. Molecular and cellular interactions in pathogenesis of sporadic Parkinson disease.Int. J. Mol. Sci.202223211304310.3390/ijms232113043 36361826
     [Google Scholar]
  72. TristB.G. HareD.J. DoubleK.L. Oxidative stress in the aging substantia nigra and the etiology of Parkinson’s disease.Aging Cell2019186e1303110.1111/acel.13031 31432604
     [Google Scholar]
  73. ZhuH. WangZ. JinJ. Parkinson’s disease-like forelimb akinesia induced by BmK I, a sodium channel modulator.Behav. Brain Res.201630816617610.1016/j.bbr.2016.04.036 27108049
     [Google Scholar]
  74. WangZ. LinY. LiuW. Voltage-gated sodium channels are involved in cognitive impairments in Parkinson’s disease-like rats.Neuroscience201941823124310.1016/j.neuroscience.2019.08.024 31473280
     [Google Scholar]
  75. RogawskiM.A. LöscherW. The neurobiology of antiepileptic drugs.Nat. Rev. Neurosci.20045755356410.1038/nrn1430 15208697
     [Google Scholar]
  76. LiuW. LaoW. ZhangR. ZhuH. Altered expression of voltage gated sodium channel Nav1.1 is involved in motor ability in MPTP-treated mice.Brain Res. Bull.202117018719810.1016/j.brainresbull.2021.02.017 33610724
     [Google Scholar]
  77. DuflocqA. BrasL.B. BullierE. CouraudF. DavenneM. Nav1.1 is predominantly expressed in nodes of Ranvier and axon initial segments.Mol. Cell. Neurosci.200839218019210.1016/j.mcn.2008.06.008 18621130
     [Google Scholar]
  78. HardimanO. van den BergL.H. Edaravone: A new treatment for ALS on the horizon?Lancet Neurol.201716749049110.1016/S1474‑4422(17)30163‑1 28522180
     [Google Scholar]
  79. PetrovD. MansfieldC. MoussyA. HermineO. ALS clinical trials review: 20 years of failure. Are we any closer to registering a new treatment?Front. Aging Neurosci.201796810.3389/fnagi.2017.00068 28382000
     [Google Scholar]
  80. HinchcliffeM. SmithA. Riluzole: Real-world evidence supports significant extension of median survival times in patients with amyotrophic lateral sclerosis.Degener. Neurol. Neuromuscul. Dis.20177617010.2147/DNND.S135748 30050378
     [Google Scholar]
  81. ChoH. ShuklaS. Role of edaravone as a treatment option for patients with amyotrophic lateral sclerosis.Pharmaceuticals20201412910.3390/ph14010029 33396271
     [Google Scholar]
  82. BlascoH. MavelS. CorciaP. GordonP.H. The glutamate hypothesis in ALS: Pathophysiology and drug development.Curr. Med. Chem.201421313551357510.2174/0929867321666140916120118 25245510
     [Google Scholar]
  83. LazarevicV. YangY. IvanovaD. FejtovaA. SvenningssonP. Riluzole attenuates the efficacy of glutamatergic transmission by interfering with the size of the readily releasable neurotransmitter pool.Neuropharmacology2018143384810.1016/j.neuropharm.2018.09.021 30222983
     [Google Scholar]
  84. CarunchioI. CurcioL. PieriM. Increased levels of p70s6 phosphorylation in the g93a mouse model of amyotrophic lateral sclerosis and in valine-exposed cortical neurons in culture.Exp. Neurol.2010226121823010.1016/j.expneurol.2010.08.033 20832409
     [Google Scholar]
  85. CarterB.C. GiesselA.J. SabatiniB.L. BeanB.P. Transient sodium current at subthreshold voltages: Activation by EPSP waveforms.Neuron20127561081109310.1016/j.neuron.2012.08.033 22998875
     [Google Scholar]
  86. ÖzdinlerP.H. BennS. YamamotoT.H. GüzelM. BrownR.H.Jr MacklisJ.D. Corticospinal motor neurons and related subcerebral projection neurons undergo early and specific neurodegeneration in hSOD1G93A transgenic ALS mice.J. Neurosci.201131114166417710.1523/JNEUROSCI.4184‑10.2011 21411657
     [Google Scholar]
  87. GeevasingaN. MenonP. ÖzdinlerP.H. KiernanM.C. VucicS. Pathophysiological and diagnostic implications of cortical dysfunction in ALS.Nat. Rev. Neurol.2016121165166110.1038/nrneurol.2016.140 27658852
     [Google Scholar]
  88. FranklinJ.P. KnockC.J. BaheerathanA. Concurrent sodium channelopathies and amyotrophic lateral sclerosis supports shared pathogenesis.Amyotroph Lateral Scler Frontot Degener2020217-862763010.1080/21678421.2020.1786128 32619119
     [Google Scholar]
  89. HiyamaT.Y. WatanabeE. OnoK. Nax channel involved in CNS sodium-level sensing.Nat. Neurosci.20025651151210.1038/nn0602‑856 11992118
     [Google Scholar]
  90. MillerP.S. GomezK. KhannaR. Peptide and peptidomimetic inhibitors targeting the interaction of collapsin response mediator protein 2 with the N-type calcium channel for pain relief.ACS Pharmacol. Transl. Sci.2024771916193610.1021/acsptsci.4c00181 39022365
     [Google Scholar]
  91. CherchiF. New insight into the role of adenosine and acetylcholine receptors on neuronal excitability and oligodendrogliogenesis: An in vitro study.In: Tuscan Doctoral Thesis in Neuroscience (XXXIII cycle).University of France20211263
     [Google Scholar]
  92. HanssonE. BjörklundU. SkiöldebrandE. RönnbäckL. Anti-inflammatory effects induced by pharmaceutical substances on inflammatory active brain astrocytes—promising treatment of neuroinflammation.J. Neuroinflammation201815132110.1186/s12974‑018‑1361‑8 30447700
     [Google Scholar]
  93. BlackJ.A. NewcombeJ. WaxmanS.G. Nav1.5 sodium channels in macrophages in multiple sclerosis lesions.Mult. Scler.201319553254210.1177/1352458512460417 22951351
     [Google Scholar]
  94. ElinderF. LiinS.I. Actions and mechanisms of polyunsaturated fatty acids on voltage-gated ion channels.Front. Physiol.201784310.3389/fphys.2017.00043 28220076
     [Google Scholar]
  95. HernándezA.C. NishigakiT. Ion currents through the voltage sensor domain of distinct families of proteins.J. Biol. Phys.202349439341310.1007/s10867‑023‑09645‑z 37851173
     [Google Scholar]
  96. MiceliF. SoldovieriM.V. AmbrosinoP. Molecular pathophysiology and pharmacology of the voltage-sensing module of neuronal ion channels.Front. Cell. Neurosci.2015925910.3389/fncel.2015.00259 26236192
     [Google Scholar]
  97. WeiF. YanL.M. SuT. Ion channel genes and epilepsy: Functional alteration, pathogenic potential, and mechanism of epilepsy.Neurosci. Bull.201733445547710.1007/s12264‑017‑0134‑1 28488083
     [Google Scholar]
  98. VillaC. CombiR. Potassium channels and human epileptic phenotypes: An updated overview.Front. Cell. Neurosci.2016108110.3389/fncel.2016.00081 27064559
     [Google Scholar]
  99. MehrotraS. PierceM.L. CaoZ. JabbaS.V. GerwickW.H. MurrayT.F. Antillatoxin-stimulated neurite outgrowth involves the brain-derived neurotrophic factor (BDNF)-tropomyosin related kinase B (TrkB) signaling pathway.J. Nat. Prod.202285356257110.1021/acs.jnatprod.1c01001 35239341
     [Google Scholar]
  100. JaworskiT. Control of neuronal excitability by GSK-3beta: Epilepsy and beyond.Biochim. Biophys. Acta Mol. Cell Res.20201867911874510.1016/j.bbamcr.2020.118745 32450268
     [Google Scholar]
  101. HouseC.D. WangB.D. CeniccolaK. Voltage-gated Na+ channel activity increases colon cancer transcriptional activity and invasion via persistent MAPK signaling.Sci. Rep.2015511154110.1038/srep11541 26096612
     [Google Scholar]
  102. EijkelkampN. LinleyJ.E. BakerM.D. Neurological perspectives on voltage-gated sodium channels.Brain201213592585261210.1093/brain/aws225 22961543
     [Google Scholar]
  103. BuckleyM.T. SunE.D. GeorgeB.M. Cell-type-specific aging clocks to quantify aging and rejuvenation in neurogenic regions of the brain.Nat. Aging20223112113710.1038/s43587‑022‑00335‑4 37118510
     [Google Scholar]
  104. TyshkovskiyA. Distinct longevity mechanisms across and within species and their association with aging.Cell2023186132929294910.1016/j.cell.2023.05.002
     [Google Scholar]
  105. HahnO. Atlas of the aging mouse brain reveals white matter as vulnerable foci.Cell2023186194117413310.1016/j.cell.2023.07.027
     [Google Scholar]
  106. LeiterO. BriciD. FletcherS.J. Platelet-derived exerkine CXCL4/platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice.Nat. Commun.2023141437510.1038/s41467‑023‑39873‑9 37587147
     [Google Scholar]
  107. GulenM.F. SamsonN. KellerA. cGAS-STING drives ageing-related inflammation and neurodegeneration.Nature2023620797337438010.1038/s41586‑023‑06373‑1 37532932
     [Google Scholar]
  108. AguadoJ. ChaggarH.K. InclánG.C. Inhibition of the cGAS‐STING pathway ameliorates the premature senescence hallmarks of Ataxia‐Telangiectasia brain organoids.Aging Cell2021209e1346810.1111/acel.13468 34459078
     [Google Scholar]
  109. ParkC. Platelet factors are induced by longevity factor klotho and enhance cognition in young and aging mice.Nat. Aging2023391067107810.1038/s43587‑023‑00468‑0
     [Google Scholar]
  110. CauwenbergheV.C. VandendriesscheC. LibertC. VandenbrouckeR.E. Caloric restriction: Beneficial effects on brain aging and Alzheimer’s disease.Mamm. Genome2016277-830031910.1007/s00335‑016‑9647‑6 27240590
     [Google Scholar]
  111. NorengS. LiT. PayandehJ. Structural pharmacology of voltage-gated sodium channels.J. Mol. Biol.20214331716696710.1016/j.jmb.2021.166967 33794261
     [Google Scholar]
  112. MüllerP. DraguhnA. EgorovA.V. Persistent sodium currents in neurons: Potential mechanisms and pharmacological blockers.Pflugers Arch.2024476101445147310.1007/s00424‑024‑02980‑7 38967655
     [Google Scholar]
  113. WarisA SirajM KhanA LinJ AsimM AlhumaydhFA A comprehensive overview of the current status and advancements in various treatment strategies against Epilepsy.ACS Pharmacol Transl Sci20244c0049410.1021/acsptsci.4c00494
     [Google Scholar]
/content/journals/cnsnddt/10.2174/0118715273347470250126185122
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Abnormality of Voltage-Gated Sodium Channels in Disease Development of the Nervous System. A Review Article
CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 24, 582 (2025); https://doi.org/10.2174/0118715273347470250126185122
/content/journals/cnsnddt/10.2174/0118715273347470250126185122
/content/journals/cnsnddt/10.2174/0118715273347470250126185122
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  • Article Type:     Review Article
Keyword(s): channelopathies; genetic mutations; nervous system disorders; neurodegeneration; pathophysiology; Voltage-gated sodium channels (VGSCs)

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