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2000
Volume 32, Issue 11
  • ISSN: 0929-8665
  • E-ISSN: 1875-5305

Abstract

Scorpion venom compounds are known to contain nucleotides, polypeptides, mucoproteins, lipids, biogenic amines, and other unidentified macromolecules. Several peptides in scorpion fluids have demonstrated a wide range of biological activities with strong specificity for their targeted sites. Margatoxin, isolated from the venom of the scorpion, exhibits desirable properties, including high selectivity, good permeability, and stability in cancer cells, which can be achieved at picomolar doses, thereby blocking voltage-gated K+ channels. This narrative review consolidates results from an extensive literature search conducted in major electronic databases up to September 2024. Important studies were identified using keywords associated with scorpion venom peptides, Kv1.3 channels, cancer treatment, and neurodegenerative disorders. The amino acids that make up Margatoxin have an effective molecular function in blocking voltage-gated K+ channels 1.3. Due to the abnormally high expression of voltage-gated K+ channel 1.3 in various types of cancers, blockers of this channel can inhibit apoptosis, metabolic changes, tumor angiogenesis, invasion, and migration. On the other hand, these channel blockers have emerged as a promising therapeutic approach for neurological disorders, such as Alzheimer’s and Parkinson’s diseases. The strong efficacy and targeted action of margatoxin further position it as a promising drug candidate. As the number of individuals affected by cancer and neurological conditions continues to rise, research into scorpion venom peptides like margatoxin may lead to innovative therapeutic options for future treatments.

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References

  1. CorrieP.G. Cytotoxic chemotherapy: Clinical aspects.Medicine2008361242810.1016/j.mpmed.2007.10.012
    [Google Scholar]
  2. FuY. ZhengS. HuangR. AnN. ZhengY. ZhangZ. LiangA. A potential strategy for high-grade gliomas: Combination treatment with lithium chloride and BmK CT.Biotechnol. Lett.201234191710.1007/s10529‑011‑0741‑2 21932030
    [Google Scholar]
  3. MoodyT.W. PradhanT. ManteyS.A. JensenR.T. DybaM. MoodyD. TarasovaN.I. MichejdaC.J. Bombesin marine toxin conjugates inhibit the growth of lung cancer cells.Life Sci.20088215-1685586110.1016/j.lfs.2008.01.019 18336841
    [Google Scholar]
  4. UzairB. Bint-e-IrshadS. KhanB.A. AzadB. MahmoodT. RehmanM.U. BragaV.A. Scorpion venom peptides as a potential source for human drug candidates.Protein Pept. Lett.201825770270810.2174/0929866525666180614114307 29921194
    [Google Scholar]
  5. Cesa-LunaC. Muñoz-RojasJ. Saab-RinconG. BaezA. Morales-GarcíaY.E. Juárez-GonzálezV.R. Quintero-HernándezV. Structural characterization of scorpion peptides and their bactericidal activity against clinical isolates of multidrug-resistant bacteria.PLoS One20191411e022243810.1371/journal.pone.0222438 31710627
    [Google Scholar]
  6. HmedB. SerriaH.T. MounirZ.K. Scorpion peptides: Potential use for new drug development.J. Toxicol.2013201395879795879710.1155/2013/958797 23843786
    [Google Scholar]
  7. BartokA. TothA. SomodiS. SzantoT.G. HajduP. PanyiG. VargaZ. Margatoxin is a non-selective inhibitor of human Kv1.3 K+ channels.Toxicon20148761610.1016/j.toxicon.2014.05.002 24878374
    [Google Scholar]
  8. SarageaP.D. Alzheimer’s Disease (AD): Environmental modifiable risk factors.Int. J. Multidiscip. Res.202464110.36948/ijfmr.2024.v06i04.26759
    [Google Scholar]
  9. CastiblancoJ. Arcos-BurgosM. AnayaJ.M. What is next after the genes for autoimmunity?BMC Med.201311119710.1186/1741‑7015‑11‑197 24107170
    [Google Scholar]
  10. CahalanM.D. DeCourseyT.E. Ion channels in immune cells. Textbook of Ion Channels ZhengJ. TrudeauM.C. CRC PressBoca Raton2023310712810.1201/9781003310310‑7
    [Google Scholar]
  11. FeskeS. WulffH. SkolnikE.Y. Ion channels in innate and adaptive immunity.Annu. Rev. Immunol.201533129135310.1146/annurev‑immunol‑032414‑112212 25861976
    [Google Scholar]
  12. TanZ.S. BeiserA.S. VasanR.S. RoubenoffR. DinarelloC.A. HarrisT.B. BenjaminE.J. AuR. KielD.P. WolfP.A. SeshadriS. Inflammatory markers and the risk of Alzheimer disease.Neurology200768221902190810.1212/01.wnl.0000263217.36439.da 17536046
    [Google Scholar]
  13. WangX. LiG. GuoJ. ZhangZ. ZhangS. ZhuY. ChengJ. YuL. JiY. TaoJ. Kv1. 3 channel as a key therapeutic target for neuroinflammatory diseases: State of the art and beyond.Front. Neurosci.202013139310.3389/fnins.2019.01393 31992966
    [Google Scholar]
  14. Garcia-CalvoM. LeonardR.J. NovickJ. StevensS.P. SchmalhoferW. KaczorowskiG.J. GarciaM.L. Purification, characterization, and biosynthesis of margatoxin, a component of Centruroides margaritatus venom that selectively inhibits voltage-dependent potassium channels.J. Biol. Chem.199326825188661887410.1016/S0021‑9258(17)46707‑X 8360176
    [Google Scholar]
  15. GeL. HoaN.T. WilsonZ. Arismendi-MorilloG. KongX.T. TajhyaR.B. BeetonC. JadusM.R. Big Potassium (BK) ion channels in biology, disease and possible targets for cancer immunotherapy.Int. Immunopharmacol.201422242744310.1016/j.intimp.2014.06.040 25027630
    [Google Scholar]
  16. RajputM. MansourS.M.G. BraunL.J. DarweeshM. ThakurN. ChaseC.C.L. Comparison of the affinity chromatography and the ion exchange chromatography in the isolation of bovine immunoglobin G.OAlib2014161510.4236/oalib.1100960
    [Google Scholar]
  17. BednarekM.A. BugianesiR.M. LeonardR.J. FelixJ.P. Chemical synthesis and structure-function studies of margatoxin, a potent inhibitor of voltage-dependent potassium channel in human T lymphocytes.Biochem. Biophys. Res. Commun.1994198261962510.1006/bbrc.1994.1090 8297371
    [Google Scholar]
  18. AnangiR. KoshyS. HuqR. BeetonC. ChuangW.J. KingG.F. Recombinant expression of margatoxin and agitoxin-2 in Pichia pastoris: An efficient method for production of KV1.3 channel blockers.PLoS One2012712e5296510.1371/journal.pone.0052965 23300835
    [Google Scholar]
  19. NaseemM.U. TajtiG. GasparA. SzantoT.G. BorregoJ. PanyiG. Optimization of Pichia pastoris expression system for high-level production of margatoxin.Front. Pharmacol.202112116
    [Google Scholar]
  20. BaronasV.A. YangR.Y. KurataH.T. Extracellular redox sensitivity of Kv1.2 potassium channels.Sci. Rep.201771914210.1038/s41598‑017‑08718‑z 28831076
    [Google Scholar]
  21. JangS.H. ChoiS.Y. RyuP.D. LeeS.Y. Anti-proliferative effect of Kv1.3 blockers in A549 human lung adenocarcinoma in vitro and in vivo.Eur. J. Pharmacol.20116511-3263210.1016/j.ejphar.2010.10.066 21087602
    [Google Scholar]
  22. ChenX. ZhangL. HeL. ZhengL. TuoB. Potassium channels as novel molecular targets in hepatocellular carcinoma.Oncol. Rep.202350418510.3892/or.2023.8622 37654193
    [Google Scholar]
  23. GoldsteinS.A.N. BockenhauerD. O’KellyI. ZilberbergN. Potassium leak channels and the KCNK family of two-p-domain subunits.Nat. Rev. Neurosci.20012317518410.1038/35058574 11256078
    [Google Scholar]
  24. DadkhahM. JafarzadehgharehziaaddinM. MolaeiS. AkbariM. GholizadehN. FathiF. Major depressive disorder: Biomarkers and biosensors.Clin. Chim. Acta202354711743710.1016/j.cca.2023.117437 37315724
    [Google Scholar]
  25. WulffH. CastleN.A. PardoL.A. Voltage-gated potassium channels as therapeutic targets.Nat. Rev. Drug Discov.2009812982100110.1038/nrd2983 19949402
    [Google Scholar]
  26. LotshawD.P. Biophysical, pharmacological, and functional characteristics of cloned and native mammalian two-pore domain K+ channels.Cell Biochem. Biophys.200747220925610.1007/s12013‑007‑0007‑8 17652773
    [Google Scholar]
  27. BeetonC. BarbariaJ. GiraudP. DevauxJ. BenolielA.M. GolaM. SabatierJ.M. BernardD. CrestM. BéraudE. Selective blocking of voltage-gated K+ channels improves experimental autoimmune encephalomyelitis and inhibits T cell activation.J. Immunol.2001166293694410.4049/jimmunol.166.2.936 11145670
    [Google Scholar]
  28. KooG.C. BlakeJ.T. TalentoA. NguyenM. LinS. SirotinaA. ShahK. MulvanyK. HoraD.Jr CunninghamP. WunderlerD.L. McManusO.B. SlaughterR. BugianesiR. FelixJ. GarciaM. WilliamsonJ. KaczorowskiG. SigalN.H. SpringerM.S. FeeneyW. Blockade of the voltage-gated potassium channel Kv1.3 inhibits immune responses in vivo.J. Immunol.19971581151205128 9164927
    [Google Scholar]
  29. DjamgozM.B. CoombesR.C. SchwabA. Ion transport and cancer: From initiation to metastasis.Philos. Trans. R. Soc. Lond. B Biol. Sci.201436916382013009210.1098/rstb.2013.0092 24493741
    [Google Scholar]
  30. RanjbariF. RashidiM.R. HemmatiS. SafariE. TajalliH. Synthesis of novel cationic photosensitizers derived from chlorin for application in photodynamic therapy of cancer.Curr. Radiopharm.202316431532510.2174/1874471016666230526153806 37246330
    [Google Scholar]
  31. FraserS.P. TesiA. BonitoB. HuiM.K.M. ArcangeliA. DjamgozM. Potassium channel blockage and invasiveness of strongly metastatic prostate and breast cancer cells.Bioelectricity20213321522010.1089/bioe.2020.0041
    [Google Scholar]
  32. KaurP. RoyS. MinochaS. ChughA. Assessing the anticancer potential of spider venom peptide Latarcin Ltc2a against triple negative breast cancer.Biochim. Biophys. Acta Biomembr.20251867718444210.1016/j.bbamem.2025.184442 40840671
    [Google Scholar]
  33. FraserS.P. GrimesJ.A. DjamgozM.B.A. Effects of voltage-gated ion channel modulators on rat prostatic cancer cell proliferation: Comparison of strongly and weakly metastatic cell lines.Prostate2000441617610.1002/1097‑0045(20000615)44:1<61::AID‑PROS9>3.0.CO;2‑3 10861759
    [Google Scholar]
  34. WoodforkK.A. WonderlinW.F. PetersonV.A. StroblJ.S. Inhibition of ATP‐sensitive potassium channels causes reversible cell‐cycle arrest of human breast cancer cells in tissue culture.J. Cell. Physiol.1995162216317110.1002/jcp.1041620202 7822427
    [Google Scholar]
  35. AndersonK.J. CormierR.T. ScottP.M. Role of ion channels in gastrointestinal cancer.World J. Gastroenterol.201925385732577210.3748/wjg.v25.i38.5732 31636470
    [Google Scholar]
  36. LeonardR.J. GarciaM.L. SlaughterR.S. ReubenJ.P. Selective blockers of voltage-gated K+ channels depolarize human T lymphocytes: Mechanism of the antiproliferative effect of charybdotoxin.Proc. Natl. Acad. Sci. USA19928921100941009810.1073/pnas.89.21.10094 1279670
    [Google Scholar]
  37. ÖnerÇ. ÇolakE. CoşanD.T. Different approaches for breast cancer: Voltage gated potassium channels and microRNAs.Commun. Fac. Sci. Univ. Ankara Ser. C Biol.201524111710.1501/commuc_0000000181
    [Google Scholar]
  38. KazamaI. Physiological significance of delayed rectifier K+ channels (Kv1.3) expressed in T lymphocytes and their pathological significance in chronic kidney disease.J. Physiol. Sci.2015651253510.1007/s12576‑014‑0331‑x 25096892
    [Google Scholar]
  39. KazamaI. MaruyamaY. MurataY. SanoM. Voltage-dependent biphasic effects of chloroquine on delayed rectifier K+-channel currents in murine thymocytes.J. Physiol. Sci.201262326727410.1007/s12576‑012‑0195‑x 22328488
    [Google Scholar]
  40. JudgeS.I.V. LeeJ.M. BeverC.T. HoffmanP.M. Voltage-gated potassium channels in multiple sclerosis: Overview and new implications for treatment of central nervous system inflammation and degeneration.J. Rehabil. Res. Dev.200643111112210.1682/JRRD.2004.09.0116 16847777
    [Google Scholar]
  41. CañasC.A. Castaño-ValenciaS. Castro-HerreraF. Pharmacological blockade of KV1.3 channel as a promising treatment in autoimmune diseases.J. Transl. Autoimmun.2022510014610.1016/j.jtauto.2022.100146 35146402
    [Google Scholar]
  42. MaezawaI. NguyenH.M. Di LucenteJ. JenkinsD.P. SinghV. HiltS. KimK. RangarajuS. LeveyA.I. WulffH. JinL.W. Kv1.3 inhibition as a potential microglia-targeted therapy for Alzheimer’s disease: preclinical proof of concept.Brain2018141259661210.1093/brain/awx346 29272333
    [Google Scholar]
  43. SarkarS. Microglial ion channels: Key players in non-cell autonomous neurodegeneration.Neurobiol. Dis.202217410586110.1016/j.nbd.2022.105861 36115552
    [Google Scholar]
  44. FominaA.F. NguyenH.M. WulffH. Kv1.3 inhibition attenuates neuroinflammation through disruption of microglial calcium signaling.Channels2021151677810.1080/19336950.2020.1853943 33356832
    [Google Scholar]
  45. LandJ. LintermansL.L. StegemanC.A. Muñoz-ElíasE.J. TarchaE.J. IadonatoS.P. HeeringaP. RutgersA. AbdulahadW.H. Kv1. 3 channel blockade modulates the effector function of B cells in granulomatosis with polyangiitis.Front. Immunol.20178120510.3389/fimmu.2017.01205 29018452
    [Google Scholar]
  46. Veytia-BucheliJ.I. Jiménez-VargasJ.M. Melchy-PérezE.I. Sandoval-HernándezM.A. PossaniL.D. RosensteinY. Kv1.3 channel blockade with the Vm24 scorpion toxin attenuates the CD4+ effector memory T cell response to TCR stimulation.Cell Commun. Signal.20181614510.1186/s12964‑018‑0257‑7 30107837
    [Google Scholar]
  47. YuanX.L. ZhaoY.P. HuangJ. LiuJ.C. MaoW.Q. YinJ. PengB.W. LiuW.H. HanS. HeX.H.A. Kv1.3 channel‐specific blocker alleviates neurological impairment through inhibiting T‐cell activation in experimental autoimmune encephalomyelitis.CNS Neurosci. Ther.2018241096797710.1111/cns.12848 29577640
    [Google Scholar]
  48. TannerM.R. TajhyaR.B. HuqR. GehrmannE.J. RodarteK.E. AtikM.A. NortonR.S. PenningtonM.W. BeetonC. Prolonged immunomodulation in inflammatory arthritis using the selective Kv1.3 channel blocker HsTX1[R14A] and its PEGylated analog.Clin. Immunol.2017180455710.1016/j.clim.2017.03.014 28389388
    [Google Scholar]
  49. GrissmerS. NguyenA.N. AiyarJ. HansonD.C. MatherR.J. GutmanG.A. KarmilowiczM.J. AuperinD.D. ChandyK.G. Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines.Mol. Pharmacol.19944561227123410.1016/S0026‑895X(25)10594‑4 7517498
    [Google Scholar]
  50. PossaniL.D. BecerrilB. DelepierreM. TytgatJ. Scorpion toxins specific for Na+‐channels.Eur. J. Biochem.1999264228730010.1046/j.1432‑1327.1999.00625.x 10491073
    [Google Scholar]
  51. GweeM.C.E. NirthananS. KhooH.E. GopalakrishnakoneP. KiniR.M. CheahL.S. Autonomic effects of some scorpion venoms and toxins.Clin. Exp. Pharmacol. Physiol.200229979580110.1046/j.1440‑1681.2002.03726.x 12165045
    [Google Scholar]
  52. JosephB. GeorgeJ. Scorpion toxins and its applications.Int. J. Toxicol. Pharmacol. Res.2012435761
    [Google Scholar]
  53. Al AzadS. ShahriyarS. MondalK.J. Margatoxin (MgTX) and its effect on immune response and disease development.Eur. Acad. Res.201644057
    [Google Scholar]
  54. CheongA. LiJ. SukumarP. KumarB. ZengF. RichesK. MunschC. WoodI.C. PorterK.E. BeechD.J. Potent suppression of vascular smooth muscle cell migration and human neointimal hyperplasia by KV1.3 channel blockers.Cardiovasc. Res.201189228228910.1093/cvr/cvq305 20884640
    [Google Scholar]
  55. BeetonC. PenningtonM.W. WulffH. SinghS. NugentD. CrossleyG. KhaytinI. CalabresiP.A. ChenC.Y. GutmanG.A. ChandyK.G. Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy of autoimmune diseases.Mol. Pharmacol.20056741369138110.1124/mol.104.008193 15665253
    [Google Scholar]
  56. ChiangE.Y. LiT. JeetS. PengI. ZhangJ. LeeW.P. DeVossJ. CaplaziP. ChenJ. WarmingS. HackosD.H. MukundS. KothC.M. GroganJ.L. Potassium channels Kv1.3 and KCa3.1 cooperatively and compensatorily regulate antigen-specific memory T cell functions.Nat. Commun.2017811464410.1038/ncomms14644 28248292
    [Google Scholar]
  57. WulffH. CalabresiP.A. AllieR. YunS. PenningtonM. BeetonC. ChandyK.G. The voltage-gated Kv1.3 K+ channel in effector memory T cells as new target for MS.J. Clin. Invest.2003111111703171310.1172/JCI16921 12782673
    [Google Scholar]
  58. NaseemM.U. TajtiG. GasparA. SzantoT.G. BorregoJ. PanyiG. Optimization of Pichia pastoris expression system for high-level production of margatoxin.Front. Pharmacol.20211273361010.3389/fphar.2021.733610 34658872
    [Google Scholar]
  59. WulffH. ZhorovB.S. K+ channel modulators for the treatment of neurological disorders and autoimmune diseases.Chem. Rev.200810851744177310.1021/cr078234p 18476673
    [Google Scholar]
  60. ChenX. FengY. QuinnR.J. PountneyD.L. RichardsonD.R. MellickG.D. MaL. Potassium channels in Parkinson’s Disease: Potential roles in its pathogenesis and innovative molecular targets for treatment.Pharmacol. Rev.202375475878810.1124/pharmrev.122.000743 36918260
    [Google Scholar]
  61. CahalanM.D. ChandyK.G. DeCourseyT.E. GuptaS. A voltage‐gated potassium channel in human T lymphocytes.J. Physiol.1985358119723710.1113/jphysiol.1985.sp015548 2580081
    [Google Scholar]
  62. SarkarS. NguyenH.M. MalovicE. LuoJ. LangleyM. PalanisamyB.N. SinghN. ManneS. NealM. GabrielleM. AbdallaA. AnantharamP. RokadD. PanickerN. SinghV. AyM. CharliA. HarischandraD. JinL.W. JinH. RangarajuS. AnantharamV. WulffH. KanthasamyA.G. Kv1.3 modulates neuroinflammation and neurodegeneration in Parkinson’s disease.J. Clin. Invest.2020130810.1172/JCI13617410.1172/JCI136174 32597830
    [Google Scholar]
  63. JennerP. Oxidative stress in Parkinson’s disease.Ann. Neurol.200353S3S26S3810.1002/ana.10483 12666096
    [Google Scholar]
  64. HirschE.C. HunotS. Neuroinflammation in Parkinson’s disease: A target for neuroprotection?Lancet Neurol.20098438239710.1016/S1474‑4422(09)70062‑6 19296921
    [Google Scholar]
  65. GoldmanS.M. Environmental toxins and Parkinson’s disease.Annu. Rev. Pharmacol. Toxicol.201454114116410.1146/annurev‑pharmtox‑011613‑135937 24050700
    [Google Scholar]
  66. BlesaJ. Trigo-DamasI. Quiroga-VarelaA. Jackson-LewisV.R. Oxidative stress and Parkinson’s disease.Front. Neuroanat.201599110.3389/fnana.2015.00091 26217195
    [Google Scholar]
  67. MaL. Gholam AzadM. DharmasivamM. RichardsonV. QuinnR.J. FengY. PountneyD.L. TonissenK.F. MellickG.D. YanatoriI. RichardsonD.R. Parkinson’s disease: Alterations in iron and redox biology as a key to unlock therapeutic strategies.Redox Biol.20214110189610.1016/j.redox.2021.101896 33799121
    [Google Scholar]
  68. ToldiG. VásárhelyiB. KaposiA. MészárosG. PánczélP. HosszufalusiN. TulassayT. TreszlA. Lymphocyte activation in type 1 diabetes mellitus: The increased significance of Kv1.3 potassium channels.Immunol. Lett.20101331354110.1016/j.imlet.2010.06.009 20603149
    [Google Scholar]
  69. HuangJ. HanS. SunQ. ZhaoY. LiuJ. YuanX. MaoW. PengB. LiuW. YinJ. HeX. Kv1.3 channel blocker (ImKTx88) maintains blood-brain barrier in experimental autoimmune encephalomyelitis.Cell Biosci.2017713110.1186/s13578‑017‑0158‑2 28596825
    [Google Scholar]
  70. RangarajuS. ChiV. PenningtonM.W. ChandyK.G. Kv1.3 potassium channels as a therapeutic target in multiple sclerosis.Expert Opin. Ther. Targets200913890992410.1517/14728220903018957 19538097
    [Google Scholar]
  71. PimentelC. M’BarekS. VisanV. GrissmerS. SampieriF. SabatierJ.M. DarbonH. FajlounZ. Chemical synthesis and 1 H‐NMR 3D structure determination of AgTx2‐MTX chimera, a new potential blocker for Kv1.2 channel, derived from MTX and AgTx2 scorpion toxins.Protein Sci.200817110711810.1110/ps.073122908 18042681
    [Google Scholar]
  72. MouhatS. VisanV. AnanthakrishnanS. WulffH. AndreottiN. GrissmerS. DarbonH. De WaardM. SabatierJ.M. K+ channel types targeted by synthetic OSK1, a toxin from Orthochirus scrobiculosus scorpion venom.Biochem. J.200538519510410.1042/BJ20041379 15588251
    [Google Scholar]
  73. Ramirez-NavarroA. GlazebrookP.A. Kane-SuttonM. PadroC. KlineD.D. KunzeD.L. Kv1.3 channels regulate synaptic transmission in the nucleus of solitary tract.J. Neurophysiol.201110562772278010.1152/jn.00494.2010 21430270
    [Google Scholar]
  74. MenesesD. VegaA.V. Torres-CruzF.M. BarralJ. KV1 and KV3 potassium channels identified at presynaptic terminals of the corticostriatal synapses in rat.Neural Plast.20162016878251810.1155/2016/8782518 27379187
    [Google Scholar]
  75. CozzolinoR. CalìG. BifulcoM. LaccettiP. A metabolically stable analogue of anandamide, Met-F-AEA, inhibits human thyroid carcinoma cell lines by activation of apoptosis.Invest. New Drugs201028211512310.1007/s10637‑009‑9221‑0 19189054
    [Google Scholar]
  76. TubertC. TaraviniI.R.E. Flores-BarreraE. SánchezG.M. ProstM.A. AvaleM.E. TsengK.Y. RelaL. MurerM.G. Decrease of a current mediated by Kv1. 3 channels causes striatal cholinergic interneuron hyperexcitability in experimental parkinsonism.Cell Rep.201616102749276210.1016/j.celrep.2016.08.016 27568555
    [Google Scholar]
  77. YangW. FengJ. WangB. CaoZ. LiW. WuY. ChenZ. BF9, the first functionally characterized snake toxin peptide with Kunitz-type protease and potassium channel inhibiting properties.J. Biochem. Mol. Toxicol.2014282768310.1002/jbt.21538 24243656
    [Google Scholar]
  78. WangT. LeeM.H. JohnsonT. AllieR. HuL. CalabresiP.A. NathA. Activated T-cells inhibit neurogenesis by releasing granzyme B: Rescue by Kv1.3 blockers.J. Neurosci.201030145020502710.1523/JNEUROSCI.0311‑10.2010 20371822
    [Google Scholar]
  79. CharolidiN. SchillingT. EderC. Microglial Kv1. 3 channels and P2Y12 receptors differentially regulate cytokine and chemokine release from brain slices of young adult and aged mice.PLoS One2015105e012846310.1371/journal.pone.0128463 26011191
    [Google Scholar]
  80. HuL. PenningtonM. JiangQ. WhartenbyK.A. CalabresiP.A. Characterization of the functional properties of the voltage-gated potassium channel Kv1.3 in human CD4+ T lymphocytes.J. Immunol.200717974563457010.4049/jimmunol.179.7.4563 17878353
    [Google Scholar]
  81. SchillingT. EderC. Amyloid-β-induced reactive oxygen species production and priming are differentially regulated by ion channels in microglia.J. Cell. Physiol.2011226123295330210.1002/jcp.22675 21321937
    [Google Scholar]
  82. YuanX. HanS. ManyandeA. GaoF. WangJ. ZhangW. TianX. Spinal voltage‐gated potassium channel Kv1.3 contributes to neuropathic pain via the promotion of microglial M1 polarization and activation of the NLRP3 inflammasome.Eur. J. Pain202327228930210.1002/ejp.2059 36440534
    [Google Scholar]
  83. RangarajuS. GearingM. JinL.W. LeveyA. Potassium channel Kv1.3 is highly expressed by microglia in human Alzheimer’s disease.J. Alzheimers Dis.201544379780810.3233/JAD‑141704 25362031
    [Google Scholar]
  84. TajtiG. WaiD.C.C. PanyiG. NortonR.S. The voltage-gated potassium channel KV1.3 as a therapeutic target for venom-derived peptides.Biochem. Pharmacol.202018111414610.1016/j.bcp.2020.114146 32653588
    [Google Scholar]
  85. YangY. HangW. LiJ. LiuT. HuY. FangF. YanD. McQuillanP.M. WangM. HuZ. Effect of general anesthetic agents on microglia.Aging Dis.20241531308132810.14336/AD.2023.1108 37962460
    [Google Scholar]
  86. Dueñas-CuellarR.A. SantanaC.J.C. MagalhãesA.C.M. PiresO.R. FontesW. CastroM.S. Scorpion toxins and ion channels: Potential applications in cancer therapy.Toxins202012532610.3390/toxins12050326 32429050
    [Google Scholar]
  87. JavedM. HussainS. KhanM.A. TajammalA. FatimaH. AmjadM. ZahidA. UmerM. AliS.A. Yaqoob, M Potential of Scorpion venom for the treatment of various diseases.Int. J. Chem. Res.2022631910.22159/ijcr.2022v6i3.204
    [Google Scholar]
  88. RazaviM. Safe and effective pharmacologic management of arrhythmias.Tex. Heart Inst. J.2005322209211 16107117
    [Google Scholar]
  89. Anti-cancer effects of voltage-gated K+ channel blockers, dendrotoxin-K and margatoxin, in Gefitinib-resistant H460 lung cancer cell line.Doctoral dissertation, Seoul National University Graduate School2014
    [Google Scholar]
  90. Galíndez-CerónJ.D. JorgeR.J.B. Chavez-AcostaM.H. JorgeA.R.C. AlvesN.T.Q. PrataM.M.G. RodriguesF.A.P. HavtA. SampaioT.L. MartinsA.M.C. Guerrero-VargasJ.A. MonteiroH.S.A. Beltrán-VidalJ.T. Renal alterations induced by the venom of Colombian scorpion Centruroides margaritatus.Curr. Top. Med. Chem.201919222049205710.2174/1568026619666190731143523 31364515
    [Google Scholar]
  91. RanjbariF. NosratA. ZaefizadehM. FathiF. Kinetic and thermodynamic study of margatoxin peptide interaction with human serum albumin: Studied by biophysical and docking methods.Int. J. Pept. Res. Ther.20243055210.1007/s10989‑024‑10633‑7
    [Google Scholar]
  92. ThirumalaivasanN. NanganS. VermaD. ShellaiahM. AliS. RajendranS. KanagarajK. PothuR. BoddulaR. RadwanA.B. Al-QahtaniN. Exploring the diverse nanomaterials employed in dental prosthesis and implant techniques: An overview.Nanotechnol. Rev.20251412025014010.1515/ntrev‑2025‑0140
    [Google Scholar]
  93. VargaZ. TajtiG. PanyiG. The Kv1.3 K+ channel in the immune system and its “precision pharmacology” using peptide toxins.Biol. Futur.2021721758310.1007/s42977‑021‑00071‑7 34554500
    [Google Scholar]
  94. VermaS. GoandU.K. HusainA. KatekarR.A. GargR. GayenJ.R. Challenges of peptide and protein drug delivery by oral route: Current strategies to improve the bioavailability.Drug Dev. Res.202182792794410.1002/ddr.21832 33988872
    [Google Scholar]
  95. SubbaiahM.A.M. RautioJ. MeanwellN.A. Prodrugs as empowering tools in drug discovery and development: Recent strategic applications of drug delivery solutions to mitigate challenges associated with lead compounds and drug candidates.Chem. Soc. Rev.20245342099221010.1039/D2CS00957A 38226865
    [Google Scholar]
  96. GopalakrishnanM. ShiehC.C. ChenJ. Potassium channels: Overview of molecular, biophysical and pharmacological properties. Voltage-Gated Ion Channels as Drug Targets TriggleD.J. GopalakrishnanM. RampeD. ZhengW. Wiley20062919321310.1002/3527608141.ch7a
    [Google Scholar]
  97. VrbnjakK. SewduthR.N. Recent advances in peptide drug discovery: Novel strategies and targeted protein degradation.Pharmaceutics20241611148610.3390/pharmaceutics16111486 39598608
    [Google Scholar]
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