Evaluation of Venom as a Promising Tool for Drug Discovery: Focusing
on Neurological Disorders

Soodeh       Omidi; Masoumeh       Mehrpouya; Morteza       Oladnabi; Abbas       Azadmehr; Fatemeh      Kazemi-Lomedasht; Najmeh       Yardehnavi
doi:10.2174/2666121701666211124151529
Abstract

Venom toxins have specific molecular targets that result in envenomated complications such as neurotoxicity. During evolution, the composition of the venom has been evolved synchronously with the evolution of molecular targets. Venom is an important tool for humans from two different perspectives; venom advantages and disadvantages. Meanwhile, clinical and pharmacological applications of venoms due to their specific targeting and modulation of physiological elements or targets are notable in various disorders. The better understanding of venoms and their composition will improve the practical applications of some toxin-based drugs in drugstoresin the future.
Keywords: Venom-based drugs, venomics, therapeutics, biochemical weapon, genomics, biological molecules.
Graphical Abstract

[1] 
Casewell NR, Wüster W, Vonk FJ, Harrison RA, Fry BG. Complex cocktails: The evolutionary novelty of venoms. Trends Ecol Evol  2013; 28(4): 219-29.
[http://dx.doi.org/10.1016/j.tree.2012.10.020] [PMID: 23219381] 
[2] 
Utkin YN. Animal venom studies: Current benefits and future developments. World J Biol Chem  2015; 6(2): 28-33.
[http://dx.doi.org/10.4331/wjbc.v6.i2.28] [PMID: 26009701] 
[3] 
Klupczynska A, Pawlak M, Kokot ZJ, Matysiak J. Application of metabolomic tools for studying low molecular-weight fraction of animal venoms and poisons. Toxins (Basel)  2018; 10(8): 306.
[http://dx.doi.org/10.3390/toxins10080306] [PMID: 30042318] 
[4] 
Kazemi-Lomedasht F, Khalaj V, Bagheri KP, Behdani M, Shahbazzadeh D. The first report on transcriptome analysis of the venom gland of Iranian scorpion, Hemiscorpius lepturus. Toxicon  2017; 125: 123-30.
[http://dx.doi.org/10.1016/j.toxicon.2016.11.261] [PMID: 27914888] 
[5] 
Jahdasani R, Jamnani FR, Behdani M, et al. Identification of the immunogenic epitopes of the whole venom component of the Hemiscorpius lepturus scorpion using the phage display peptide library. Toxicon  2016; 124: 83-93.
[http://dx.doi.org/10.1016/j.toxicon.2016.11.247] [PMID: 27845058] 
[6] 
Torabi E, Asgari S, Khalaj V, et al. Corrigendum to" The first report on transcriptome analysis of the venom gland of Iranian scorpion, Hemiscorpius lepturus"[Toxicon 125 (2017) 123-130]. Toxicon  2017; 128: 60.
[http://dx.doi.org/10.1016/j.toxicon.2017.01.012] [PMID: 28192687] 
[7] 
Tasoulis T, Isbister GK. A review and database of snake venom proteomes. Toxins (Basel)  2017; 9(9): 290.
[http://dx.doi.org/10.3390/toxins9090290] [PMID: 28927001] 
[8] 
Ruiming Z, Yibao M, Yawen H, et al. Comparative venom gland transcriptome analysis of the scorpion Lychas mucronatus reveals intraspecific toxic gene diversity and new venomous components. BMC Genomics  2010; 11(1): 452.
[http://dx.doi.org/10.1186/1471-2164-11-452] [PMID: 20663230] 
[9] 
Abdel-Rahman MA, Omran MAA, Abdel-Nabi IM, Ueda H, McVean A. Intraspecific variation in the Egyptian scorpion Scorpio maurus palmatus venom collected from different biotopes. Toxicon  2009; 53(3): 349-59.
[http://dx.doi.org/10.1016/j.toxicon.2008.12.007] [PMID: 19103215] 
[10] 
Ma Y, He Y, Zhao R, Wu Y, Li W, Cao Z. Extreme diversity of scorpion venom peptides and proteins revealed by transcriptomic analysis: implication for proteome evolution of scorpion venom arsenal. J Proteomics  2012; 75(5): 1563-76.
[http://dx.doi.org/10.1016/j.jprot.2011.11.029] [PMID: 22155128] 
[11] 
Zhang Y. Why do we study animal toxins? Zool Res  2015; 36(4): 183-222.https://pubmed.ncbi.nlm.nih.gov/26228472/
[PMID: 26228472] 
[12] 
Cushman DW, Ondetti MA. History of the design of captopril and related inhibitors of angiotensin converting enzyme. Hypertension  1991; 17(4): 589-92.
[http://dx.doi.org/10.1161/01.HYP.17.4.589] [PMID: 2013486] 
[13] 
Ching AT, Paes Leme AF, Zelanis A, et al. Venomics profiling of Thamnodynastes strigatus unveils matrix metalloproteinases and other novel proteins recruited to the toxin arsenal of rear-fanged snakes. J Proteome Res  2012; 11(2): 1152-62.
[http://dx.doi.org/10.1021/pr200876c] [PMID: 22168127] 
[14] 
Kazemi-Lomedasht F, Oghalaie A, Behdani M, Shahbazzadeh D. Anti-tumor activity of Iranian cobra snake (Naja oxiana) venom on lung cancer cell line. Health Biotechnol Biopharm  2019; 3(1): 57-63.
[15] 
Oghalaie A, Kazemi-Lomedasht F, Zareinejad MR, Shahbazzadeh D. Antiadhesive and cytotoxic effect of Iranian Vipera lebetina snake venom on lung epithelial cancer cells. J Family Med Prim Care  2017; 6(4): 780-3.
[http://dx.doi.org/10.4103/jfmpc.jfmpc_208_17] [PMID: 29564263] 
[16] 
Oghalaie A, Behdani M, Yardehnavi N, Shahbazzadeh D, Kazemi-Lomedasht F. Cytotoxicity, anti-adhesive and anti-angiogenic effects of Caspian Cobra snake (Naja oxiana) venom on human endothelial cells. Health Biotechno Biopharm  2017; 1(1): 53-62.
[17] 
Peigneur S, Tytgat J. Toxins in drug discovery and pharmacology. Toxins (Basel)  2018; 10(3): 126.
[http://dx.doi.org/10.3390/toxins10030126] [PMID: 29547537] 
[18] 
Albuquerque EX, Pereira EF, Alkondon M, Rogers SW. Mammalian nicotinic acetylcholine receptors: From structure to function. Physiol Rev  2009; 89(1): 73-120.
[http://dx.doi.org/10.1152/physrev.00015.2008] [PMID: 19126755] 
[19] 
Durmus N, Gültürk S, Kaya T, Demir T, Parlak M, Altun A. Evaluation of effects of T and N type calcium channel blockers on the electroencephalogram recordings in Wistar Albino Glaxo/Rij rats, an absence epilepsy model. Indian J Pharmacol  2015; 47(1): 34-8.
[http://dx.doi.org/10.4103/0253-7613.150324] [PMID: 25821308] 
[20] 
Wu J, Jiang H, Bi Q, et al. Apamin-mediated actively targeted drug delivery for treatment of spinal cord injury: More than just a concept. Mol Pharm  2014; 11(9): 3210-22.
[http://dx.doi.org/10.1021/mp500393m] [PMID: 25098949] 
[21] 
Kaplan N, Morpurgo N, Linial M. Novel families of toxin-like peptides in insects and mammals: A computational approach. J Mol Biol  2007; 369(2): 553-66.
[http://dx.doi.org/10.1016/j.jmb.2007.02.106] [PMID: 17433819] 
[22] 
Anastasi A, Erspamer V, Bucci M. Isolation and structure of bombesin and alytesin, 2 analogous active peptides from the skin of the European amphibians Bombina and Alytes. Experientia  1971; 27(2): 166-7.
[http://dx.doi.org/10.1007/BF02145873] [PMID: 5544731] 
[23] 
Zhang HP, Xiao Z, Cilz NI, Hu B, Dong H, Lei S. Bombesin facilitates GABAergic transmission and depresses epileptiform activity in the entorhinal cortex. Hippocampus  2014; 24(1): 21-31.
[http://dx.doi.org/10.1002/hipo.22191] [PMID: 23966303] 
[24] 
Ranawaka UK, Lalloo DG, de Silva HJ. Neurotoxicity in snakebite- the limits of our knowledge. PLoS Negl Trop Dis  2013; 7(10): e2302.
[http://dx.doi.org/10.1371/journal.pntd.0002302] [PMID: 24130909] 
[25] 
Lonati D, Giampreti A, Rossetto O, et al. Neurotoxicity of European viperids in Italy: Pavia Poison Control Centre case series 2001-2011. Clin Toxicol (Phila)  2014; 52(4): 269-76.
[http://dx.doi.org/10.3109/15563650.2014.904046] [PMID: 24708390] 
[26] 
Vu TT, Stafford AR, Leslie BA, Kim PY, Fredenburgh JC, Weitz JI. Batroxobin binds fibrin with higher affinity and promotes clot expansion to a greater extent than thrombin. J Biol Chem  2013; 288(23): 16862-71.
[http://dx.doi.org/10.1074/jbc.M113.464750] [PMID: 23612970] 
[27] 
Yitao H, Kefu M, Bingshan T, et al. Effects of batroxobin with continuous transcranial Doppler monitoring in patients with acute cerebral stroke: A randomized controlled trial. Echocardiography  2014; 31(10): 1283-92.
[http://dx.doi.org/10.1111/echo.12559] [PMID: 24684297] 
[28] 
Chen W, Carvalho LP, Chan MY, Kini RM, Kang TS. Fasxiator, a novel factor XIa inhibitor from snake venom, and its site-specific mutagenesis to improve potency and selectivity. J Thromb Haemost  2015; 13(2): 248-61.
[http://dx.doi.org/10.1111/jth.12797] [PMID: 25418421] 
[29] 
Eriksson L, Saxelin R, Röhl S, et al. Glucagon-like peptide-1 receptor activation does not affect re-endothelialization but reduces intimal hyperplasia via direct effects on smooth muscle cells in a nondiabetic model of arterial injury. J Vasc Res  2015; 52(1): 41-52.
[http://dx.doi.org/10.1159/000381097] [PMID: 25966620] 
[30] 
Hwang DS, Kim SK, Bae H. Therapeutic effects of bee venom on immunological and neurological diseases. Toxins (Basel)  2015; 7(7): 2413-21.
[http://dx.doi.org/10.3390/toxins7072413] [PMID: 26131770] 
[31] 
Park S, Baek H, Jung KH, et al. Bee venom phospholipase A2 suppresses allergic airway inflammation in an ovalbumin-induced asthma model through the induction of regulatory T cells. Immun Inflamm Dis  2015; 3(4): 386-97.
[http://dx.doi.org/10.1002/iid3.76] [PMID: 26734460] 
[32] 
Son DJ, Lee JW, Lee YH, Song HS, Lee CK, Hong JT. Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds. Pharmacol Ther  2007; 115(2): 246-70.
[http://dx.doi.org/10.1016/j.pharmthera.2007.04.004] [PMID: 17555825] 
[33] 
Li L, Huang J, Lin Y. Snake venoms in cancer therapy: Past, present and future. Toxins (Basel)  2018; 10(9): 346.
[http://dx.doi.org/10.3390/toxins10090346] [PMID: 30158426] 
[34] 
Ma R, Mahadevappa R, Kwok HF. Venom-based peptide therapy: Insights into anti-cancer mechanism. Oncotarget  2017; 8(59): 100908-30.
[http://dx.doi.org/10.18632/oncotarget.21740] [PMID: 29246030] 
[35] 
Dardevet L, Rani D, Aziz TA, et al. Chlorotoxin: A helpful natural scorpion peptide to diagnose glioma and fight tumor invasion. Toxins (Basel)  2015; 7(4): 1079-101.
[http://dx.doi.org/10.3390/toxins7041079] [PMID: 25826056] 
[36] 
Zhao L, Shi X, Zhao J. Chlorotoxin-conjugated nanoparticles for targeted imaging and therapy of glioma. Curr Top Med Chem  2015; 15(13): 1196-208.
[http://dx.doi.org/10.2174/1568026615666150330110822] [PMID: 25858130] 
[37] 
Mattson MP. Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol  2000; 1(2): 120-9.
[http://dx.doi.org/10.1038/35040009] [PMID: 11253364] 
[38] 
Chung ES, Lee G, Lee C, et al. Bee venom phospholipase A2, a novel Foxp3+ regulatory T cell inducer, protects dopaminergic neurons by modulating neuroinflammatory responses in a mouse model of Parkinson’s disease. J Immunol  2015; 195(10): 4853-60.
[http://dx.doi.org/10.4049/jimmunol.1500386] [PMID: 26453752] 
[39] 
Yin SM, Zhao D, Yu DQ, et al. Neuroprotection by scorpion venom heat resistant peptide in 6-hydroxydopamine rat model of early-stage Parkinson’s disease. Sheng Li Xue Bao  2014; 66(6): 658-66.https://pubmed.ncbi.nlm.nih.gov/25516514/
[PMID: 25516514] 
[40] 
Wang T, Wang SW, Zhang Y, et al. Scorpion venom heat-resistant peptide (SVHRP) enhances neurogenesis and neurite outgrowth of immature neurons in adult mice by up-regulating brain-derived neurotrophic factor (BDNF). PLoS One  2014; 9(10): e109977.
[http://dx.doi.org/10.1371/journal.pone.0109977] [PMID: 25299676] 
[41] 
Xu H, An D, Yin SM, et al. The alterations of apoptosis factor Bcl-2/Bax in the early Parkinson’s disease rats and the protective effect of scorpion venom derived activity peptide. Chung Kuo Ying Yung Sheng Li Hsueh Tsa Chih  2015; 31(3): 225-9.https://pubmed.ncbi.nlm.nih.gov/26387182/
[PMID: 26387182] 
[42] 
Martins NM, Santos NA, Sartim MA, Cintra AC, Sampaio SV, Santos AC. A tripeptide isolated from Bothrops atrox venom has neuroprotective and neurotrophic effects on a cellular model of Parkinson’s disease. Chem Biol Interact  2015; 235: 10-6.
[http://dx.doi.org/10.1016/j.cbi.2015.04.004] [PMID: 25868679] 
[43] 
Jin J, Kang HM, Jung J, Jeong JW, Park C. Related expressional change of HIF-1α to the neuroprotective activity of exendin-4 in transient global ischemia. Neuroreport  2014; 25(1): 65-70.
[http://dx.doi.org/10.1097/WNR.0000000000000046] [PMID: 24201448] 
[44] 
Darsalia V, Hua S, Larsson M, et al. Exendin-4 reduces ischemic brain injury in normal and aged type 2 diabetic mice and promotes microglial M2 polarization. PLoS One  2014; 9(8): e103114.
[http://dx.doi.org/10.1371/journal.pone.0103114] [PMID: 25101679] 
[45] 
Yang EJ, Jiang JH, Lee SM, et al. Bee venom attenuates neuroinflammatory events and extends survival in amyotrophic lateral sclerosis models. J Neuroinflammation  2010; 7(1): 69.
[http://dx.doi.org/10.1186/1742-2094-7-69] [PMID: 20950451] 
[46] 
Lee MJ, Jang M, Choi J, et al. Bee venom acupuncture alleviates experimental autoimmune encephalomyelitis by upregulating regulatory T cells and suppressing Th1 and Th17 responses. Mol Neurobiol  2016; 53(3): 1419-45.
[http://dx.doi.org/10.1007/s12035-014-9012-2] [PMID: 25579380] 
[47] 
Dhanak AC, Rishipathak DD, Gide D. Multiple Sclerosis & it’s treatment with Alpha-Cobratoxin: A review. Int J Pharm Tech Res  2010; 2(1): 740-9.
[48] 
Fujii T, Mashimo M, Moriwaki Y, et al. Expression and function of the cholinergic system in immune cells. Front Immunol  2017; 8: 1085.
[http://dx.doi.org/10.3389/fimmu.2017.01085] [PMID: 28932225] 
[49] 
Khalil WK, Assaf N, ElShebiney SA, Salem NA. Neuroprotective effects of bee venom acupuncture therapy against rotenone-induced oxidative stress and apoptosis. Neurochem Int  2015; 80: 79-86.
[http://dx.doi.org/10.1016/j.neuint.2014.11.008] [PMID: 25481089] 
[50] 
McEntire DM, Kirkpatrick DR, Dueck NP, et al. Pain transduction: A pharmacologic perspective. Expert Rev Clin Pharmacol  2016; 9(8): 1069-80.
[http://dx.doi.org/10.1080/17512433.2016.1183481] [PMID: 27137678] 
[51] 
Ramírez D, Gonzalez W, Fissore RA, Carvacho I. Conotoxins as tools to understand the physiological function of voltage-gated calcium (CaV) channels. Mar Drugs  2017; 15(10): 313.
[http://dx.doi.org/10.3390/md15100313] [PMID: 29027927] 
[52] 
Lebbe EK, Peigneur S, Wijesekara I, Tytgat J. Conotoxins targeting nicotinic acetylcholine receptors: an overview. Mar Drugs  2014; 12(5): 2970-3004.
[http://dx.doi.org/10.3390/md12052970] [PMID: 24857959] 
[53] 
Li RA, Tomaselli GF. Using the deadly μ-conotoxins as probes of voltage-gated sodium channels. Toxicon  2004; 44(2): 117-22.
[http://dx.doi.org/10.1016/j.toxicon.2004.03.028] [PMID: 15246758] 
[54] 
Miljanich GP. Ziconotide: Neuronal calcium channel blocker for treating severe chronic pain. Curr Med Chem  2004; 11(23): 3029-40.
[http://dx.doi.org/10.2174/0929867043363884] [PMID: 15578997] 
[55] 
Di Cesare Mannelli L, Cinci L, Micheli L, et al. α-conotoxin RgIA protects against the development of nerve injury-induced chronic pain and prevents both neuronal and glial derangement. Pain  2014; 155(10): 1986-95.
[http://dx.doi.org/10.1016/j.pain.2014.06.023] [PMID: 25008370] 
[56] 
Chang E, Chen X, Kim M, Gong N, Bhatia S, Luo ZD. Differential effects of voltage-gated calcium channel blockers on calcium channel alpha-2-delta-1 subunit protein-mediated nociception. Eur J Pain  2015; 19(5): 639-48.
[http://dx.doi.org/10.1002/ejp.585] [PMID: 25158907] 
[57] 
Green BR, Bulaj G, Norton RS. Structure and function of μ-conotoxins, peptide-based sodium channel blockers with analgesic activity. Future Med Chem  2014; 6(15): 1677-98.
[http://dx.doi.org/10.4155/fmc.14.107] [PMID: 25406007] 
[58] 
Deng M, Luo X, Xiao Y, et al. Huwentoxin-XVI, an analgesic, highly reversible mammalian N-type calcium channel antagonist from Chinese tarantula Ornithoctonus huwena. Neuropharmacology  2014; 79: 657-67.
[http://dx.doi.org/10.1016/j.neuropharm.2014.01.017] [PMID: 24467846] 
[59] 
Liu X, Li C, Chen J, et al. AGAP, a new recombinant neurotoxic polypeptide, targets the voltage-gated calcium channels in rat small diameter DRG neurons. Biochem Biophys Res Commun  2014; 452(1): 60-5.
[http://dx.doi.org/10.1016/j.bbrc.2014.08.051] [PMID: 25148943] 
[60] 
Tonello R, Rigo F, Gewehr C, et al. Action of Phα1β, a peptide from the venom of the spider Phoneutria nigriventer, on the analgesic and adverse effects caused by morphine in mice. J Pain  2014; 15(6): 619-31.
[http://dx.doi.org/10.1016/j.jpain.2014.02.007] [PMID: 24607814] 
[61] 
Rosa F, Trevisan G, Rigo FK, et al. Phα1β, a peptide from the venom of the spider Phoneutria nigriventer shows antinociceptive effects after continuous infusion in a neuropathic pain model in rats. Anesth Analg  2014; 119(1): 196-202.
[http://dx.doi.org/10.1213/ANE.0000000000000249] [PMID: 24836473] 
[62] 
Liu JK. The history of monoclonal antibody development - Progress, remaining challenges and future innovations. Ann Med Surg (Lond)  2014; 3(4): 113-6.
[http://dx.doi.org/10.1016/j.amsu.2014.09.001] [PMID: 25568796] 
[63] 
Xiao Y, Bingham JP, Zhu W, Moczydlowski E, Liang S, Cummins TR. Tarantula huwentoxin-IV inhibits neuronal sodium channels by binding to receptor site 4 and trapping the domain ii voltage sensor in the closed configuration. J Biol Chem  2008; 283(40): 27300-13.
[http://dx.doi.org/10.1074/jbc.M708447200] [PMID: 18628201] 
[64] 
Cardoso FC, Dekan Z, Rosengren KJ, et al. Identification and characterization of ProTx-III [μ-TRTX-Tp1a], a new voltage-gated sodium channel inhibitor from venom of the tarantula Thrixopelma pruriens. Mol Pharmacol  2015; 88(2): 291-303.
[http://dx.doi.org/10.1124/mol.115.098178] [PMID: 25979003] 
[65] 
Liu Y, Tang J, Zhang Y, et al. Synthesis and analgesic effects of μ-TRTX-Hhn1b on models of inflammatory and neuropathic pain. Toxins (Basel)  2014; 6(8): 2363-78.
[http://dx.doi.org/10.3390/toxins6082363] [PMID: 25123556] 
[66] 
Lim BS, Moon HJ, Li DX, et al. Effect of bee venom acupuncture on oxaliplatin-induced cold allodynia in rats. Evid Based Complement Alternat Med  2013; 2013: 369324.
[http://dx.doi.org/10.1155/2013/369324] [PMID: 24058370] 
[67] 
Lee JH, Li DX, Yoon H, et al. Serotonergic mechanism of the relieving effect of bee venom acupuncture on oxaliplatin-induced neuropathic cold allodynia in rats. BMC Complement Altern Med  2014; 14(1): 471.
[http://dx.doi.org/10.1186/1472-6882-14-471] [PMID: 25481535] 
[68] 
Roh DH, Kwon YB, Kim HW, et al. Acupoint stimulation with diluted bee venom (apipuncture) alleviates thermal hyperalgesia in a rodent neuropathic pain model: Involvement of spinal alpha 2-adrenoceptors. J Pain  2004; 5(6): 297-303.
[http://dx.doi.org/10.1016/j.jpain.2004.05.003] [PMID: 15336634] 
[69] 
Lim SM, Lee SH. Effectiveness of bee venom acupuncture in alleviating post-stroke shoulder pain: A systematic review and meta-analysis. J Integr Med  2015; 13(4): 241-7.
[http://dx.doi.org/10.1016/S2095-4964(15)60178-9] [PMID: 26165368] 
[70] 
Chen L, Deltheil T, Turle-Lorenzo N, et al. SK channel blockade reverses cognitive and motor deficits induced by nigrostriatal dopamine lesions in rats. Int J Neuropsychopharmacol  2014; 17(8): 1295-306.
[http://dx.doi.org/10.1017/S1461145714000236] [PMID: 24661728] 
[71] 
Peng Y, Lu K, Li Z, et al. Blockade of Kv1.3 channels ameliorates radiation-induced brain injury. Neuro-oncol  2014; 16(4): 528-39.
[http://dx.doi.org/10.1093/neuonc/not221] [PMID: 24305723] 
[72] 
Waqar M, Batool S. In silico analysis of binding of neurotoxic venom ligands with acetylcholinesterase for therapeutic use in treatment of Alzheimer’s disease. J Theor Biol  2015; 372: 107-17.
[http://dx.doi.org/10.1016/j.jtbi.2015.02.028] [PMID: 25747777] 
[73] 
Balsara R, Dang A, Donahue DL, Snow T, Castellino FJ. Conantokin-G attenuates detrimental effects of NMDAR hyperactivity in an ischemic rat model of stroke. PLoS One  2015; 10(3): e0122840.
[http://dx.doi.org/10.1371/journal.pone.0122840] [PMID: 25822337] 
[74] 
Vargas LS, Lara MV, Gonçalves R, et al. The intrahippocampal infusion of crotamine from Crotalus durissus terrificus venom enhances memory persistence in rats. Toxicon  2014; 85: 52-8.
[http://dx.doi.org/10.1016/j.toxicon.2014.04.017] [PMID: 24813333] 
[75] 
Liang YX, Zhang ZY, Zhang R. Antinociceptive effect of najanalgesin from naja naja atra in a neuropathic pain model via inhibition of c-jun NH2-terminal kinase. Chin Med J (Engl)  2015; 128(17): 2340-5.
[http://dx.doi.org/10.4103/0366-6999.163397] [PMID: 26315082] 
[76] 
Lee SM, Yang EJ, Choi SM, Kim SH, Baek MG, Jiang JH. Effects of bee venom on glutamate-induced toxicity in neuronal and glial cells. Evid Based Complement Alternat Med  2012; 2012: 368196.
[http://dx.doi.org/10.1155/2012/368196] [PMID: 21904562] 
[77] 
Zambelli VO, Fernandes AC, Gutierrez VP, et al. Peripheral sensitization increases opioid receptor expression and activation by crotalphine in rats. PLoS One  2014; 9(3): e90576.
[http://dx.doi.org/10.1371/journal.pone.0090576] [PMID: 24594607] 
[78] 
Aviles-Olmos I, Dickson J, Kefalopoulou Z, et al. Exenatide and the treatment of patients with Parkinson’s disease. J Clin Invest  2013; 123(6): 2730-6.
[http://dx.doi.org/10.1172/JCI68295] [PMID: 23728174] 
[79] 
Aviles-Olmos I, Dickson J, Kefalopoulou Z, et al. Motor and cognitive advantages persist 12 months after exenatide exposure in Parkinson’s disease. J Parkinsons Dis  2014; 4(3): 337-44.
[http://dx.doi.org/10.3233/JPD-140364] [PMID: 24662192] 
Rights & Permissions Print Cite
Article Metrics
30
1
DOI https://dx.doi.org/10.2174/2666121701666211124151529	Print ISSN 2666-1217
Publisher Name Bentham Science Publisher	Online ISSN 2666-1225
Venoms and Toxins

Evaluation of Venom as a Promising Tool for Drug Discovery: Focusing on Neurological Disorders

Abstract Play Pause

Graphical Abstract

Related Articles

Abstract
