{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:57:03Z","timestamp":1791928623786,"version":"4.3.4"},"reference-count":133,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation","award":["0101-2019-0019"],"award-info":[{"award-number":["0101-2019-0019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Snake venoms as tools for hunting are primarily aimed at the most vital systems of the prey, especially the nervous and circulatory systems. In general, snakes of the Elapidae family produce neurotoxic venoms comprising of toxins targeting the nervous system, while snakes of the Viperidae family and most rear-fanged snakes produce hemotoxic venoms directed mainly on blood coagulation. However, it is not all so clear. Some bites by viperids results in neurotoxic signs and it is now known that hemotoxic venoms do contain neurotoxic components. For example, viperid phospholipases A2 may manifest pre- or\/and postsynaptic activity and be involved in pain and analgesia. There are other neurotoxins belonging to diverse families ranging from large multi-subunit proteins (e.g., C-type lectin-like proteins) to short peptide neurotoxins (e.g., waglerins and azemiopsin), which are found in hemotoxic venoms. Other neurotoxins from hemotoxic venoms include baptides, crotamine, cysteine-rich secretory proteins, Kunitz-type protease inhibitors, sarafotoxins and three-finger toxins. Some of these toxins exhibit postsynaptic activity, while others affect the functioning of voltage-dependent ion channels. This review represents the first attempt to systematize data on the neurotoxins from \u201cnon-neurotoxic\u201d snake venom. The structural and functional characteristic of these neurotoxins affecting diverse targets in the nervous system are considered.<\/jats:p>","DOI":"10.3390\/ijms24032919","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T02:35:10Z","timestamp":1675391710000},"page":"2919","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["What Are the Neurotoxins in Hemotoxic Snake Venoms?"],"prefix":"10.3390","volume":"24","author":[{"given":"Alexey","family":"Osipov","sequence":"first","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4609-970X","authenticated-orcid":false,"given":"Yuri","family":"Utkin","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"ref_1","first-page":"60","article-title":"Chapter 8\u2014Ophidia (Snakes)","volume":"Volume 8","author":"Miller","year":"2015","journal-title":"Fowler\u2019s Zoo and Wild Animal Medicine"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wallach, V., Williams, K.L., and Boundy, J. (2014). Snakes of the World: A Catalogue of Living and Extinct Species, CRC Press. [1st ed.].","DOI":"10.1201\/b16901"},{"key":"ref_3","unstructured":"Wikipedia (2023, January 10). List of Dangerous Snakes. Available online: https:\/\/en.wikipedia.org\/wiki\/List_of_dangerous_snakes."},{"key":"ref_4","unstructured":"World Health Organization (WHO) (2023, January 10). Snakebite Information and Data Platform, Available online: https:\/\/www.who.int\/teams\/control-of-neglected-tropical-diseases\/snakebite-envenoming\/snakebite-information-and-data-platform\/overview#tab=tab_1,2020."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.tips.2020.05.006","article-title":"Causes and consequences of snake venom variation","volume":"41","author":"Casewell","year":"2020","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_6","first-page":"2443","article-title":"Coevolution of diet and prey-specific venom activity supports the role of selection in snake venom evolution","volume":"276","author":"Barlow","year":"2009","journal-title":"Proc. Biol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ranawaka, U.K., Lalloo, D.G., and de Silva, H.J. (2013). Neurotoxicity in snakebite\u2014The limits of our knowledge. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002302"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4","DOI":"10.32607\/actanaturae.11375","article-title":"Cardiovascular effects of snake toxins: Cardiotoxicity and cardioprotection","volume":"13","author":"Averin","year":"2021","journal-title":"Acta Nat."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"279","DOI":"10.3389\/fevo.2019.00279","article-title":"Venoms of rear-fanged snakes: New proteins and novel activities","volume":"7","author":"Modahl","year":"2019","journal-title":"Front. Ecol. Evol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.toxicon.2015.03.001","article-title":"Snake venomics of monocled cobra (Naja kaouthia) and investigation of human IgG response against venom toxins","volume":"99","author":"Laustsen","year":"2015","journal-title":"Toxicon"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"727756","DOI":"10.3389\/fphar.2021.727756","article-title":"Snake venom proteomics of Samar cobra (Naja samarensis) from the Southern Philippines: Short alpha-neurotoxins as the dominant lethal component weakly cross-neutralized by the Philippine cobra antivenom","volume":"12","author":"Palasuberniam","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1080\/14789450.2019.1609945","article-title":"Quantitative proteomic analysis of venom from Southern India common krait (Bungarus caeruleus) and identification of poorly immunogenic toxins by immune-profiling against commercial antivenom","volume":"16","author":"Patra","year":"2019","journal-title":"Expert Rev. Proteom."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.toxicon.2015.08.026","article-title":"Quantitative proteomic analysis of Vietnamese krait venoms: Neurotoxins are the major components in Bungarus multicinctus and phospholipases A2 in Bungarus fasciatus","volume":"107","author":"Ziganshin","year":"2015","journal-title":"Toxicon"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.2174\/0929867043363820","article-title":"Dendrotoxins: Structure-activity relationships and effects on potassium ion channels","volume":"11","author":"Harvey","year":"2004","journal-title":"Curr. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"114168","DOI":"10.1016\/j.bcp.2020.114168","article-title":"Snake three-finger \u03b1-neurotoxins and nicotinic acetylcholine receptors: Molecules, mechanisms and medicine","volume":"181","author":"Nirthanan","year":"2020","journal-title":"Biochem Pharmacol."},{"key":"ref_16","first-page":"101164","article-title":"Venom proteomic analysis of medically important Nigerian viper Echis ocellatus and Bitis arietans snake species","volume":"28","author":"Dingwoke","year":"2021","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"giac121","DOI":"10.1093\/gigascience\/giac121","article-title":"High-throughput proteomics and in vitro functional characterization of the 26 medically most important elapids and vipers from sub-Saharan Africa","volume":"11","author":"Nguyen","year":"2022","journal-title":"Gigascience"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/j.1600-0404.2011.01593.x","article-title":"Neurological complications of venomous snake bites: A review","volume":"125","year":"2012","journal-title":"Acta Neurol. Scand."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.toxicon.2021.06.009","article-title":"Synergistic effect of serine protease inhibitors and a bothropic antivenom in reducing local hemorrhage and coagulopathy caused by Bothrops jararaca venom","volume":"199","author":"Silva","year":"2021","journal-title":"Toxicon"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.toxicon.2005.02.029","article-title":"Hemorrhage induced by snake venom metalloproteinases: Biochemical and biophysical mechanisms involved in microvessel damage","volume":"45","author":"Rucavado","year":"2005","journal-title":"Toxicon"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s12959-016-0113-1","article-title":"Anti-thrombotic agents derived from snake venom proteins","volume":"14","author":"Huang","year":"2016","journal-title":"Thromb. J."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Tian, H., Liu, M., Li, J., Xu, R., Long, C., Li, H., Mwangi, J., Lu, Q., Lai, R., and Shen, C. (2020). Snake C-type lectins potentially contribute to the prey immobilization in Protobothrops mucrosquamatus and Trimeresurus stejnegeri venoms. Toxins, 12.","DOI":"10.3390\/toxins12020105"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.neuro.2010.11.007","article-title":"First clinical experiences about the neurotoxic envenomings inflicted by lowland populations of the Balkan adder, Vipera berus bosniensis","volume":"32","author":"Malina","year":"2011","journal-title":"Neurotoxicology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s12640-016-9650-4","article-title":"Neurotoxicity in Sri Lankan Russell\u2019s Viper (Daboia russelii) Envenoming is Primarily due to U1-viperitoxin-Dr1a, a Pre-Synaptic Neurotoxin","volume":"31","author":"Silva","year":"2017","journal-title":"Neurotox. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"411","DOI":"10.3109\/15563650.2016.1143556","article-title":"Neurotoxicity in Russell\u2019s viper (Daboia russelii) envenoming in Sri Lanka: A clinical and neurophysiological study","volume":"54","author":"Silva","year":"2016","journal-title":"Clin. Toxicol. (Phila)"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1097\/NEN.0b013e318188c2d7","article-title":"Neurotoxicity of ammodytoxin a in the envenoming bites of Vipera ammodytes ammodytes","volume":"67","author":"Logonder","year":"2008","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.toxicon.2017.12.053","article-title":"Extending knowledge of the clinical picture of Balkan adder (Vipera berus bosniensis) envenoming: The first photographically-documented neurotoxic case from South-Western Hungary","volume":"143","author":"Varga","year":"2018","journal-title":"Toxicon"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"269","DOI":"10.3109\/15563650.2014.904046","article-title":"Neurotoxicity of European viperids in Italy: Pavia Poison Control Centre case series 2001\u20132011","volume":"52","author":"Lonati","year":"2014","journal-title":"Clin. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"w30085","DOI":"10.4414\/SMW.2021.w30085","article-title":"Indigenous venomous snakebites in Switzerland: Analysis of reports to the National Poisons Information Centre over 22 years","volume":"151","author":"Fuchs","year":"2021","journal-title":"Swiss Med. Wkly."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ferquel, E., de Haro, L., Jan, V., Guillemin, I., Jourdain, S., Teyni\u00e9, A., d\u2019Alayer, J., and Choumet, V. (2007). Reappraisal of Vipera aspis venom neurotoxicity. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0001194"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sahyoun, C., Krezel, W., Mattei, C., Sabatier, J.M., Legros, C., Fajloun, Z., and Rima, M. (2022). Neuro- and cardiovascular activities of Montivipera bornmuelleri snake venom. Biology, 11.","DOI":"10.3390\/biology11060888"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/S0196-0644(97)70111-2","article-title":"Successful treatment of crotalid-induced neurotoxicity with a new polyspecific crotalid Fab antivenom","volume":"30","author":"Clark","year":"1997","journal-title":"Ann. Emerg. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1191\/0960327103ht392oa","article-title":"Hematological, hemostatic and clinical chemistry disturbances induced by Crotalus durissus terrificus snake venom in dogs","volume":"22","author":"Tomy","year":"2003","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_34","first-page":"269","article-title":"Pit viper snakebite in the United States","volume":"6","author":"Clement","year":"1978","journal-title":"J. Fam. Pract."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1002\/cber.19380710527","article-title":"Schlangengifte III. Mitteilung: Reiningung und Krystallisation des Klapperschlangengiftes","volume":"71B","author":"Slotta","year":"1938","journal-title":"Ber. Dtsch. Chem. Ges."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"873","DOI":"10.7150\/ijbs.68093","article-title":"Secreted phospholipases A2\u2014Not just enzymes: Revisited","volume":"18","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Murakami, M., Sato, H., and Taketomi, Y. (2020). Updating phospholipase A2 biology. Biomolecules, 10.","DOI":"10.3390\/biom10101457"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1388-1981(00)00105-0","article-title":"The expanding superfamily of phospholipase A2 enzymes: Classification and characterization","volume":"1488","author":"Six","year":"2000","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1021\/bi00402a036","article-title":"Crotoxin, a phospholipase A2 neurotoxin from the South American rattlesnake Crotalus durissus terrificus: Purification of several isoforms and comparison of their molecular structure and of their biological activities","volume":"27","author":"Faure","year":"1988","journal-title":"Biochemistry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.toxicon.2012.05.009","article-title":"Crystallographic characterization of functional sites of crotoxin and ammodytoxin, potent \u03b2-neurotoxins from Viperidae venom","volume":"60","author":"Faure","year":"2012","journal-title":"Toxicon"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.toxicon.2007.07.025","article-title":"Understanding the molecular mechanism underlying the presynaptic toxicity of secreted phospholipases A2","volume":"50","author":"Pungercar","year":"2007","journal-title":"Toxicon"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.toxicon.2014.06.019","article-title":"Understanding the molecular mechanism underlying the presynaptic toxicity of secreted phospholipases A(2): An update","volume":"89","year":"2014","journal-title":"Toxicon"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.neuro.2012.12.009","article-title":"L-type voltage-dependent calcium channel is involved in the snake venom group IA secretory phospholipase A2-induced neuronal apoptosis","volume":"35","author":"Yagami","year":"2013","journal-title":"Neurotoxicology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.expneurol.2009.07.017","article-title":"Ultrastructural evidence for the uptake of a neurotoxic snake venom phospholipase A2 into mammalian motor nerve terminals","volume":"219","author":"Logonder","year":"2009","journal-title":"Exp. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ober\u010dkal, J., Kova\u010di\u010d, L., \u0160ribar, J., Leonardi, A., Dolinar, K., Pucer Jane\u017e, A., and Kri\u017eaj, I. (2015). On the role of protein disulfide isomerase in the retrograde cell transport of secreted phospholipases A2. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120692"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41598-018-36461-6","article-title":"The neurotoxic secreted phospholipase A2 from the Vipera a. ammodytes venom targets cytochrome c oxidase in neuronal mitochondria","volume":"9","author":"Petan","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ivanu\u0161ec, A., \u0160ribar, J., Verani\u010d, P., and Kri\u017eaj, I. (2022). The phospholipase activity of ammodytoxin, a prototype snake venom \u03b2-neurotoxin, is not obligatory for cell internalisation and translocation to mitochondria. Toxins, 14.","DOI":"10.3390\/toxins14060375"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxicon.2009.10.025","article-title":"Understanding the in vitro neuromuscular activity of snake venom Lys49 phospholipase A2 homologues","volume":"55","author":"Gallacci","year":"2010","journal-title":"Toxicon"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/j.1742-7843.2004.pto_950405.x","article-title":"The presynaptic activity of bothropstoxin-I, a myotoxin from Bothrops jararacussu snake venom","volume":"95","author":"Leite","year":"2004","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/jmbi.1998.1987","article-title":"Crystal structure of agkistrodotoxin, a phospholipase A2-type presynaptic neurotoxin from Agkistrodon halys pallas","volume":"282","author":"Tang","year":"1998","journal-title":"J. Mol. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1016\/j.toxicon.2008.03.031","article-title":"Mapping the structural determinants of presynaptic neurotoxicity of snake venom phospholipases A2","volume":"51","author":"Prijatelj","year":"2008","journal-title":"Toxicon"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"11627","DOI":"10.1016\/S0021-9258(17)39077-4","article-title":"A comparison of the crystal structures of phospholipase A2 from bovine pancreas and Crotalus atrox venom","volume":"260","author":"Renetseder","year":"1985","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.biochi.2010.09.021","article-title":"Mutagenesis analyses explore residues responsible for the neurotoxic and anticoagulant activities of Trimucrotoxin, a pit-viper venom Asn6-phospholipase A2","volume":"93","author":"Tsai","year":"2011","journal-title":"Biochimie"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Nemecz, D., Ostrowski, M., Ravatin, M., Saul, F., and Faure, G. (2020). Crystal structure of isoform CBd of the basic phospholipase A2 subunit of Crotoxin: Description of the structural framework of CB for interaction with protein targets. Molecules, 25.","DOI":"10.2210\/pdb6tmy\/pdb"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.toxicon.2014.04.008","article-title":"Crotoxin from Crotalus durissus terrificus snake venom induces the release of glutamate from cerebrocortical synaptosomes via N and P\/Q calcium channels","volume":"85","author":"Gomes","year":"2014","journal-title":"Toxicon"},{"key":"ref_56","first-page":"629","article-title":"Crotoxin-induced behavioral effects in rats","volume":"29","author":"Moreira","year":"1996","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1097\/00001756-200212030-00029","article-title":"beta-Agkistrodotoxin inhibition of Ca2+-dependent release of glutamate, aspartate, glycine and gamma-aminobutyric acid from cerebrocortical synaptosomes following its binding to synaptic membrane","volume":"13","author":"Zhang","year":"2002","journal-title":"Neuroreport"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.toxicon.2012.06.003","article-title":"Recognition of Vipera ammodytes meridionalis neurotoxin vipoxin and its components using phage-displayed scFv and polyclonal antivenom sera","volume":"60","author":"Stoyanova","year":"2012","journal-title":"Toxicon"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.toxicon.2011.02.013","article-title":"An unusual phospholipase A2 from puff adder Bitis arietans venom\u2014A novel blocker of nicotinic acetylcholine receptors","volume":"57","author":"Vulfius","year":"2011","journal-title":"Toxicon"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Vulfius, C.A., Kasheverov, I.E., Starkov, V.G., Osipov, A.V., Andreeva, T.V., Filkin, S.Y., Gorbacheva, E.V., Astashev, M.E., Tsetlin, V.I., and Utkin, Y.N. (2014). Inhibition of nicotinic acetylcholine receptors, a novel facet in the pleiotropic activities of snake venom phospholipases A2. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115428"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Vulfius, C.A., Kasheverov, I.E., Kryukova, E.V., Spirova, E.N., Shelukhina, I.V., Starkov, V.G., Andreeva, T.V., Faure, G., Zouridakis, M., and Tsetlin, V.I. (2017). Pancreatic and snake venom presynaptically active phospholipases A2 inhibit nicotinic acetylcholine receptors. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0186206"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.cbpc.2014.11.005","article-title":"Biochemical and pharmacological characterization of three toxic phospholipase A2s from Daboia russelii snake venom","volume":"168","author":"Kumar","year":"2015","journal-title":"Comp. Biochem. Physiol. C Toxicol. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.taap.2017.08.021","article-title":"Neuromuscular paralysis by the basic phospholipase A2 subunit of crotoxin from Crotalus durissus terrificus snake venom needs its acid chaperone to concurrently inhibit acetylcholine release and produce muscle blockage","volume":"334","author":"Cavalcante","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/S0041-0101(03)00007-2","article-title":"Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: Pharmacological mediation and molecular determinants","volume":"41","author":"Chacur","year":"2003","journal-title":"Toxicon"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Zambelli, V.O., Picolo, G., Fernandes, C.A.H., Fontes, M.R.M., and Cury, Y. (2017). Secreted phospholipases A2 from animal venoms in pain and analgesia. Toxins, 9.","DOI":"10.3390\/toxins9120406"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.toxicon.2006.04.008","article-title":"Opiate and acetylcholine-independent analgesic actions of crotoxin isolated from Crotalus durissus terrificus venom","volume":"48","author":"Zhang","year":"2006","journal-title":"Toxicon"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.pbb.2008.08.016","article-title":"The analgesic effect of crotoxin on neuropathic pain is mediated by central muscarinic receptors and 5-lipoxygenase-derived mediators","volume":"91","author":"Amorim","year":"2008","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.toxicon.2007.08.009","article-title":"Inhibitory effect of crotoxin on the pain-evoked discharge of neurons in thalamic parafascicular nucleus in rats","volume":"51","author":"Zhu","year":"2008","journal-title":"Toxicon"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.toxicon.2013.07.019","article-title":"Antinociceptive activity of crotoxin in the central nervous system: A functional Magnetic Resonance Imaging study","volume":"74","author":"Esser","year":"2013","journal-title":"Toxicon"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Sant\u2019Anna, M.B., Lopes, F.S.R., Kimura, L.F., Giardini, A.C., Sant\u2019Anna, O.A., and Picolo, G. (2019). Crotoxin conjugated to SBA-15 nanostructured mesoporous silica induces long-last analgesic effect in the neuropathic pain model in mice. Toxins, 11.","DOI":"10.3390\/toxins11120679"},{"key":"ref_71","first-page":"1","article-title":"Analysis of nociceptive effects of neurotoxic phospholipase A2 from Vipera nikolskii venom in mice","volume":"4","author":"Dyachenko","year":"2013","journal-title":"J. Venom Res."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Li, D., Kim, W., Shin, D., Jung, Y., Bae, H., and Kim, S.K. (2016). Preventive effects of bee venom derived phospholipase A2 on oxaliplatin-induced neuropathic pain in mice. Toxins, 8.","DOI":"10.3390\/toxins8010027"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"14140","DOI":"10.1073\/pnas.1009128107","article-title":"Bothrops snake myotoxins induce a large efflux of ATP and potassium with spreading of cell damage and pain","volume":"107","author":"Caccin","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","first-page":"E2524","article-title":"Lys49 myotoxin from the Brazilian lancehead pit viper elicits pain through regulated ATP release","volume":"114","author":"Zhang","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4331\/wjbc.v10.i1.17","article-title":"Last decade update for three-finger toxins: Newly emerging structures and biological activities","volume":"10","author":"Utkin","year":"2019","journal-title":"World J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/0041-0101(87)90167-X","article-title":"Isolation and pharmacological characterization of a new alpha-neurotoxin (alpha-AgTx) from venom of the viper Agkistrodon halys (Pallas)","volume":"25","author":"Jiang","year":"1987","journal-title":"Toxicon"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1034\/j.1399-3011.2002.02969.x","article-title":"Isolation and characterization of a novel postsynaptic\/cytotoxic neurotoxin from Daboia russelli russelli venom","volume":"59","author":"Shelke","year":"2002","journal-title":"J. Pept. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1002\/jbt.21486","article-title":"Purification, characterization, and chemical modification of neurotoxic peptide from Daboia russelii snake venom of India","volume":"27","author":"Venkatesh","year":"2013","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1534\/genetics.106.056515","article-title":"Lachesis muta (Viperidae) cDNAs reveal diverging pit viper molecules and scaffolds typical of cobra (Elapidae) venoms: Implications for snake toxin repertoire evolution","volume":"173","author":"Ching","year":"2006","journal-title":"Genetics"},{"key":"ref_80","first-page":"18","article-title":"Toxin transcripts in Crotalus atrox venom and in silico structures of toxins","volume":"10","author":"Jia","year":"2020","journal-title":"J. Venom Res."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Doley, R., Pahari, S., Mackessy, S.P., and Kini, R.M. (2008). Accelerated exchange of exon segments in Viperid three-finger toxin genes (Sistrurus catenatus edwardsii; Desert Massasauga). BMC Evol. Biol., 8.","DOI":"10.1186\/1471-2148-8-196"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Babenko, V.V., Ziganshin, R.H., Weise, C., Dyachenko, I., Shaykhutdinova, E., Murashev, A.N., Zhmak, M., Starkov, V., Hoang, A.N., and Tsetlin, V. (2020). Novel bradykinin-potentiating peptides and three-finger toxins from viper venom: Combined NGS venom gland transcriptomics and quantitative venom proteomics of the Azemiops feae viper. Biomedicines, 8.","DOI":"10.3390\/biomedicines8080249"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1134\/S1607672918020205","article-title":"The first recombinant viper three-finger toxins: Inhibition of muscle and neuronal nicotinic acetylcholine receptors","volume":"479","author":"Makarova","year":"2018","journal-title":"Dokl. Biochem. Biophys."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Junqueira-de-Azevedo, I.L., Campos, P.F., Ching, A.T., and Mackessy, S.P. (2016). Colubrid venom composition: An -omics perspective. Toxins, 8.","DOI":"10.3390\/toxins8080230"},{"key":"ref_85","first-page":"155","article-title":"Partial purification of acetylcholine receptor binding components from the Duvernoy\u2019s secretions of blanding\u2019s tree snake (Boiga blandingi) and the mangrove snake (Boiga dendrophila)","volume":"8","author":"Broaders","year":"1999","journal-title":"J. Nat. Toxins"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1007\/s00239-003-2497-3","article-title":"Isolation of a neurotoxin (\u03b1-colubritoxin) from a nonvenomous Colubrid: Evidence for early origin of venom in snakes","volume":"57","author":"Fry","year":"2003","journal-title":"J. Mol. Evol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jprot.2018.08.004","article-title":"Transcriptome-facilitated proteomic characterization of rear-fanged snake venoms reveal abundant metalloproteinases with enhanced activity","volume":"187","author":"Modahl","year":"2018","journal-title":"J. Proteomics"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/0041-0101(91)90107-3","article-title":"Characterization and amino acid sequences of two lethal peptides isolated from venom of Wagler\u2019s pit viper, Trimeresurus wagleri","volume":"29","author":"Weinstein","year":"1991","journal-title":"Toxicon"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/0041-0101(92)90047-9","article-title":"Molecular properties and structure-function relationships of lethal peptides from venom of Wagler\u2019s pit viper, Trimeresurus wagleri","volume":"30","author":"Schmidt","year":"1992","journal-title":"Toxicon"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s00239-016-9764-6","article-title":"Viper venom Botox: The molecular origin and evolution of the waglerin peptides used in anti-wrinkle skin cream","volume":"84","author":"Debono","year":"2017","journal-title":"J. Mol. Evol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/0041-0101(94)00134-T","article-title":"A study on the cause of death due to waglerin-I, a toxin from Trimeresurus wagleri","volume":"33","author":"Lin","year":"1995","journal-title":"Toxicon"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"5433","DOI":"10.1074\/jbc.M109232200","article-title":"Identification of residues at the alpha and epsilon subunit interfaces mediating species selectivity of Waglerin-1 for nicotinic acetylcholine receptors","volume":"277","author":"Molles","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_93","first-page":"543","article-title":"Waglerin-1 selectively blocks the epsilon form of the muscle nicotinic acetylcholine receptor","volume":"289","author":"McArdle","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/j.1600-0773.1992.tb00508.x","article-title":"A novel peptide toxin from Trimeresurus wagleri acts pre- and post-synaptically to block transmission at the rat neuromuscular junction","volume":"70","author":"Aiken","year":"1992","journal-title":"Pharmacol. Toxicol."},{"key":"ref_95","first-page":"74","article-title":"Waglerin-1 modulates gamma-aminobutyric acid activated current of murine hypothalamic neurons","volume":"282","author":"Ye","year":"1997","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0006-8993(99)01668-6","article-title":"Waglerin-1 inhibits GABA(A) current of neurons in the nucleus accumbens of neonatal rats","volume":"837","author":"Ye","year":"1999","journal-title":"Brain Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"27079","DOI":"10.1074\/jbc.M112.363051","article-title":"Azemiopsin from Azemiops feae viper venom, a novel polypeptide ligand of nicotinic acetylcholine receptor","volume":"287","author":"Utkin","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Shelukhina, I.V., Zhmak, M.N., Lobanov, A.V., Ivanov, I.A., Garifulina, A.I., Kravchenko, I.N., Rasskazova, E.A., Salmova, M.A., Tukhovskaya, E.A., and Rykov, V.A. (2018). Azemiopsin, a selective peptide antagonist of muscle nicotinic acetylcholine receptor: Preclinical evaluation as a local muscle relaxant. Toxins, 10.","DOI":"10.3390\/toxins10010034"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1134\/S1607672919040021","article-title":"Encapsulation of neurotoxins, blockers of nicotinic acetylcholine receptors, in nanomaterials based on sulfated polysaccharides","volume":"487","author":"Nguyen","year":"2019","journal-title":"Dokl. Biochem. Biophys."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.toxicon.2016.08.020","article-title":"Peptides from puff adder Bitis arietans venom, novel inhibitors of nicotinic acetylcholine receptors","volume":"121","author":"Vulfius","year":"2016","journal-title":"Toxicon"},{"key":"ref_101","first-page":"23","article-title":"Snake C-type lectin-like proteins inhibit nicotinic acetylcholine receptors","volume":"10","author":"Kryukova","year":"2020","journal-title":"J. Venom Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.toxicon.2004.05.023","article-title":"Structure and function of snake venom cysteine-rich secretory proteins","volume":"44","author":"Yamazaki","year":"2004","journal-title":"Toxicon"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.toxlet.2016.12.003","article-title":"Investigating possible biological targets of Bj-CRP, the first cysteine-rich secretory protein (CRISP) isolated from Bothrops jararaca snake venom","volume":"265","author":"Lodovicho","year":"2017","journal-title":"Toxicol. Lett."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.ijbiomac.2019.08.108","article-title":"First report on BaltCRP, a cysteine-rich secretory protein (CRISP) from Bothrops alternatus venom: Effects on potassium channels and inflammatory processes","volume":"140","author":"Bernardes","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s00204-010-0597-6","article-title":"Characterization of toxins from the broadbanded water snake Helicops angulatus (Linnaeus, 1758): Isolation of a cysteine-rich secretory protein, helicopsin","volume":"85","author":"Estrella","year":"2011","journal-title":"Arch. Toxicol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1046\/j.1432-1033.2002.02940.x","article-title":"Cloning and characterization of novel snake venom proteins that block smooth muscle contraction","volume":"269","author":"Yamazaki","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0003-9861(03)00028-6","article-title":"Wide distribution of cysteine-rich secretory proteins in snake venoms: Isolation and cloning of novel snake venom cysteine-rich secretory proteins","volume":"412","author":"Yamazaki","year":"2003","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0014-5793(03)00693-8","article-title":"Adaptive evolution in the snake venom Kunitz\/BPTI protein family","volume":"547","author":"Zupunski","year":"2003","journal-title":"FEBS Lett."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.toxicon.2017.03.011","article-title":"Pathophysiological significance and therapeutic applications of snake venom protease inhibitors","volume":"131","author":"Thakur","year":"2017","journal-title":"Toxicon"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.toxicon.2014.06.016","article-title":"Pharmacological properties and pathophysiological significance of a Kunitz-type protease inhibitor (Rusvikunin-II) and its protein complex (Rusvikunin complex) purified from Daboia russelii russelii venom","volume":"89","author":"Mukherjee","year":"2014","journal-title":"Toxicon"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.toxicon.2020.09.015","article-title":"The first Kunitz-type proteins from a viperid venom that potentiate neuromuscular transmission","volume":"187","author":"Drofenik","year":"2020","journal-title":"Toxicon"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1016\/S0041-0101(98)00117-2","article-title":"The analgesic activity of crotamine, a neurotoxin from Crotalus durissus terrificus (South American rattlesnake) venom: A biochemical and pharmacological study","volume":"36","author":"Mancin","year":"1998","journal-title":"Toxicon"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Park, J.Y., Do, B.H., Lee, J.S., Yang, H.C., Nguyen, A.N., Krupa, M., Kim, C.J., Jang, Y.J., and Choe, H. (2021). Antinociceptive and anti-inflammatory effects of recombinant crotamine in mouse models of pain. Toxins, 13.","DOI":"10.3390\/toxins13100707"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0014-2999(98)00152-6","article-title":"Tension generation and increase of voltage-activated sodium current by crotamine","volume":"348","author":"Matavel","year":"1998","journal-title":"Eur. J. Pharmacol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.toxicon.2007.04.026","article-title":"Crotamine inhibits preferentially fast-twitching muscles but is inactive on sodium channels","volume":"50","author":"Rizzi","year":"2007","journal-title":"Toxicon"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"14972","DOI":"10.1073\/pnas.0904465106","article-title":"Selective reciprocity in antimicrobial activity versus cytotoxicity of hBD-2 and crotamine","volume":"106","author":"Yount","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1124\/mol.112.078188","article-title":"Crotamine pharmacology revisited: Novel insights based on the inhibition of KV channels","volume":"82","author":"Peigneur","year":"2012","journal-title":"Mol. Pharmacol."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Lima, S.C., Porta, L.C., Lima, \u00c1.D.C., Campeiro, J.D., Meurer, Y., Teixeira, N.B., Duarte, T., Oliveira, E.B., Picolo, G., and Godinho, R.O. (2018). Pharmacological characterization of crotamine effects on mice hind limb paralysis employing both ex vivo and in vivo assays: Insights into the involvement of voltage-gated ion channels in the crotamine action on skeletal muscles. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006700"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1002\/mus.23714","article-title":"Beneficial effect of crotamine in the treatment of myasthenic rats","volume":"47","author":"Sanchez","year":"2013","journal-title":"Muscle Nerve"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/978-1-0716-1752-6_6","article-title":"A Native CPP from rattlesnake with therapeutic and theranostic properties","volume":"2383","author":"Porta","year":"2022","journal-title":"Methods Mol. Biol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.toxicon.2020.06.017","article-title":"In vivo effects of the association of the psychoactive phenotiazine thioridazine on antitumor activity and hind limb paralysis induced by the native polypeptide crotamine","volume":"185","author":"Porta","year":"2020","journal-title":"Toxicon"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2828","DOI":"10.1007\/s00018-005-5286-x","article-title":"Endothelin-like peptides","volume":"62","author":"Ducancel","year":"2005","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e13077","DOI":"10.14814\/phy2.13077","article-title":"Activation of neuronal endothelin B receptors mediates pressor response through alpha-1 adrenergic receptors","volume":"5","author":"Becker","year":"2017","journal-title":"Physiol. Rep."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1016\/S0006-291X(88)80987-2","article-title":"Characterization and localization of a novel neuroreceptor for the peptide sarafotoxin","volume":"157","author":"Ambar","year":"1988","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/0041-0101(92)90540-L","article-title":"Activity of sarafotoxin\/endothelin peptides in the heart and brain of lower vertebrates","volume":"30","author":"Bdolah","year":"1992","journal-title":"Toxicon"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/glia.440050402","article-title":"Activation of endothelin receptors by sarafotoxin regulates Ca2+ homeostasis in cerebellar astrocytes","volume":"5","author":"Holzwarth","year":"1992","journal-title":"Glia"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.bbrc.2019.12.091","article-title":"Crystal structure of human endothelin ETB receptor in complex with sarafotoxin S6b","volume":"528","author":"Izume","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_128","first-page":"1033","article-title":"Phase I and pharmacokinetics study of crotoxin (cytotoxic PLA(2), NSC-624244) in patients with advanced cancer","volume":"8","author":"Cura","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1007\/s00210-021-02103-4","article-title":"Acute toxicity, antinociceptive, and anti-inflammatory activities of the orally administered crotamine in mice","volume":"394","author":"Moreira","year":"2021","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_130","unstructured":"Utkin, Y.N., Andreeva, T.V., Osipov, A.V., Shelukhina, I.V., Kudryavtsev, D.S., Tukhovskaya, E.A., Ivanov, I.A., Tsetlin, V.I., Egorova, N.S., and Slashcheva, G.A. Method for the treatment of muscular dystonia. (RU 2 704 815), Russian Patent, filed 11 November 2017, and issued 31 October 2019."},{"key":"ref_131","first-page":"285","article-title":"Acetylcholinesterase from snake venom as a model for its nerve and muscle counterpart","volume":"8","author":"Cousin","year":"1999","journal-title":"J. Nat. Toxins"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.bbagen.2017.01.004","article-title":"Protein toxins of the Echis coloratus viper venom directly activate TRPV1","volume":"1861","author":"Geron","year":"2017","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"100130","DOI":"10.1016\/j.toxcx.2022.100130","article-title":"Proteomic insight into the venom composition of the largest European rear-fanged snake, Malpolon monspessulanus monspessulanus","volume":"15","author":"Koua","year":"2022","journal-title":"Toxicon X"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2919\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:22:31Z","timestamp":1760120551000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2919"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,2]]},"references-count":133,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24032919"],"URL":"https:\/\/doi.org\/10.3390\/ijms24032919","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,2]]}}}