Neurotoxins
Some components of venoms, called neurotoxins, affect the nervous system. The main site of snake neurotoxins is the neuromuscular junction, and they are either: (1) pre-synaptic neurotoxins irreversibly damaging the presynaptic terminal; or (2) post-synaptic neurotoxins that bind to the nicotinic acetylcholine receptor. Neuromuscular paralysis due to snake envenoming is common by elapid snakes such as kraits, cobras, coral snakes and many others.
Alpha-neurotoxins are a large group, with over 100 postsynaptic neurotoxins having been identified and sequenced. α-neurotoxins attack the Nicotinic acetylcholine receptors of cholinergic neurons. They mimic the shape of the acetylcholine molecule therefore fit into the receptors, as a consequence block the ACh flow & is responsible for feeling of numbness and paralysis. Dendrotoxins inhibit neurotransmissions by blocking the exchange of positive and negative ions across the neuronal membrane lead to no nerve impulse, thereby paralysing the nerves.
| Venom Components | Types of toxin | Toxin activity | Functions (Target/Action) | Family/ Species | References (PubMed ID, Others) |
|---|---|---|---|---|---|
| Acetylcholinesterase | Neurotoxin | Anticancer | Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions | Torpedo californica | 3753747 |
| Alpha-elapitoxin-Nk2a | Neurotoxin | Anticancer | The monomeric form binds with high affinity to muscular and neuronal alpha-7/CHRNA7 nicotinic acetylcholine receptors (nAChR). Causes paralysis by preventing acetylcholine binding to the nAChR. In mice lung cancer, causes reduction of tumor growth | Naja kaouthia | 18381281 |
| C-type lectin (Calcium-dependent lectin) | Neurotoxin | Anticancer | Shows high hemagglutinating activity. In mice model it caused edema and increased vascular permeability. An effective inhibitor of cell growth in renal and pancreatic cancer cell lines, human breast and ovarian carcinoma, glioblastoma | Bothrops jararacussu | 16309723, 10628348, 11478954 |
| Acidic phospholipaseA2 | Neurotoxin, Cytotoxin, Hemotytic | Anticancer, Anti-coagulant | Anticoagulant activities, hemolytic and cytotoxic activities. Inhibits cell migration in human skin melanoma cells and reduces tumor lung colonization of melanoma cells in BALB/c mice | Daboia ruselli siamensis | 22091349 |
| Cytotoxin drCT1 (Three-finger cytotoxin) | Neurotoxin, Cytotoxin, Cardiotoxin, Myotoxin | Anticancer, Anti-proliferative | It has antiproliferative, cytotoxic and apoptotic activities. This protein possess anticancer potential. Also it shows neurotoxicity, cardiotoxicity and myotoxicity | Daboia russelii ruselli | 17055549, 16511326 |
| PhospholipaseA2 | Neurotoxin | Antitumor | PLA2 has a weak enzymatic activity. Inhibits neuromuscular transmission by blocking acetylcholine release from the nerve termini. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides | Naja nigricollis, Bungarus fasciatus, Ophiophagus Hannah | 17166178, 6784277, 2089739, 700923, 9028866, 12217659 |
| Alpha-elapitoxin-(Nk2a, Nno2a.Ls2a) | Neurotoxicity | Neurotoxin | The monomeric form binds with high affinity to muscular and neuronal alpha-7/CHRNA7 nicotinic acetylcholine receptors (nAChR). Causes paralysis by preventing acetylcholine binding to the nAChR. The homodimeric form binds with low affinity to muscular and | Naja kaouthia, Naja oxiana, Laticauda semifasciata | 18381281, 6771288, 6553056, 2086254, 9053737, 9305882, 9840221, 10574958, 10852927, 18067132, 11867717, 6930640, 2279844, 1317211, 12133834, 15791209, 9920490, 12957382, 4616684, 8555211 |
| Short neurotoxin (A,B, C, D) | Neurotoxicity | Neurotoxin | Binds to muscle nicotinic acetylcholine receptor (nAChR) and inhibit acetylcholine from binding to the receptor, thereby impairing neuromuscular transmission | Hydrophis schistosus, Naja oxiana, Naja annulifera, Naja pallid, Naja mossambica, Naja nivea, Hydrophis lapemoides, Aipysurus laevis, Dendroaspis polylepis polylepis, Dendroaspis viridis | 4850498, 4747603, 8504813, 923577, 9305882, 1332755, 12538890, 6615431, 4995745, 5033401, 2847926, 1433289, 4091794, 4112538 |
| Short neurotoxin (1,2, 3,4,5,6, 7) (OH-35, OKI-Ed) | Neurotoxicity | Neurotoxin | Binds with high affinity to muscle nicotinic acetylcholine receptor (nAChR) and hinders acetylcholine binding to the receptor, thereby impairing neuromuscular transmission. Competes with the binding of alpha-bungarotoxin on muscle AChR (from Torpedo) with | Pseudonaja textilis, Hydrophis cyanocinctus | 10518793, 10818230, 16284125, 4830190, 8447823, 4855008, 21133350, 10497260 |
| Long neurotoxin (1, 2, 3,4, 20) Long neurotoxin homolog (Pa ID, OH-5, OH-56, OH-37, OH-34) | Neurotoxicity | Neurotoxin | Binds with high affinity to muscular nicotinic acetylcholine receptors (nAChRs), whereas it binds with a low affinity. Inhibits carbachol-induced muscle contraction in a reversible manner | Ophiophagus Hannah, Demansia vestigiata, Drysdalia coronoides, Pseudechis australis, Naja anchietae | 14559085, 16284125, 16261251, 5033401 |
| Weak neurotoxin (5,6,8,10, WNTX34, NNAM2) | Neurotoxicity | Neurotoxin | Binds with low affinity to muscular (alpha-1-beta-1-epsilon-delta/CHRNA1-CHRNB1-CHRNE-CHRND) and very low affinity to neuronal (alpha7) nicotinic acetylcholine receptor | Naja sputatrix, Ophiophagus hannah, Naja atra, Laticauda semifasciata | 9838137, 12199703, 14572646, 16689684, 24297900, 2060629 |
| Kappa-2/3-bungarotoxin | Neurotoxicity | Neurotoxin | Postsynaptic neurotoxin that binds and inhibits neuronal nicotinic acetylcholine receptors (nAChR) with high affinity (IC50<100 nM). Is a selective, and slowly reversible antagonist of alpha-3/CHRNA3-containing and some alpha-4/CHRNA4-containing AChRs | Bungarus multicinctus | 2315018, 12403176, 2322821 |
| Erabutoxin (a, b,c) | Neurotoxicity | Neurotoxin | Binds with high affinity to muscular nicotinic acetylcholine receptors (nAChRs) and with low affinity to neuronal alpha-7 nAChRs and inhibit acetylcholine from binding to the receptor, thereby impairing neuromuscular transmission. Produces peripheral para | Laticauda semifasciata | 9305882, 9840221, 2249684, 12957382, 4664580, 5166329, 588261 |
| Cobrotoxin (II, b, c) | Neurotoxicity | Neurotoxin | Binds to muscle nicotinic acetylcholine receptor (nAChR) and inhibit acetylcholine from binding to the receptor, thereby impairing neuromuscular transmission. Has a higher toxicity than cobrotoxin-b. Produces peripheral paralysis by blocking neuromuscular | Naja atra, Naja kaouthia | 9367842, 5820687, 8448165, 5533659, 12039691, 11904231 |
| Cysteine-rich protein (pseudecin, LEI1, pseudechetoxin-like, ablomin, trifling, ophanin, catrin) | Neurotoxicity | Neurotoxin | Blocks olfactory (CNGA2) and retinal (CNGA1) CNG channel currents. Blocks contraction of smooth muscle elicited by high potassium-induced depolarization, but does not block caffein-stimulated contraction. May target voltage-gated calcium channels on smoot | Pseudechis porphyriacus, Philodryas olfersii, Trimeresurus stejnegeri, Leioheterodon madagascariensis, Pseudonaja textilis, Gloydius blomhoffii, Protobothrops flavoviridis, Ophiophagus Hannah, Crotalus atrox | 12234174, 16857193, 16292255, 24297900, 16261251, 16284125 |
| Taicatoxin, alpha-neurotoxin-like component | Neurotoxicity | Neurotoxin | The heterotrimer blocks the voltage-dependent L-type calcium channels (Cav1/CACNA1) from the heart, and the small conductance calcium-activated potassium channels (KCa2/KCNN) in the chromaffin cells and in the brain | Oxyuranus scutellatus | 8901456, 9242659, 15855042 |