nervous tissue in the brain, significantly reducing the potential invasive harm caused by tumors. conotoxin conotoxins represent a category of poisons produced by the marine cone snail, and are capable of inhibiting the activity of a number of ion channels such as calcium, sodium, or potassium channels. in many cases, the toxins released by the different types of cone snails include a range of different types of conotoxins, which may be specific for different ion channels, thus creating a venom capable of widespread nerve function interruption. one of the unique forms of conotoxins, ω-conotoxin (ω-cgtx) is highly specific for ca channels and has shown usefulness in isolating them from a system. as calcium flux is necessary for proper excitability of a cell, any significant inhibition could prevent a large amount of functionality. significantly, ω-cgtx is capable of long term binding to and inhibition of voltage-dependent calcium channels located in the membranes of neurons but not those of muscle cells. botulinum toxin mechanism of botulinum toxin neurotoxicity botulinum toxin (btx) is a group of neurotoxins consisting of eight distinct compounds, referred to as btx-a,b,c,d,e,f,g,h, which are produced by the bacterium clostridium botulinum and lead to muscular paralysis. a notably unique feature of btx is its relatively common therapeutic use in treating dystonia and spasticity disorders, as well as in inducing muscular atrophy despite being the most poisonous substance known. btx functions peripherally to inhibit acetylcholine (ach) release at the neuromuscular junction through degradation of the snare proteins required for ach vesicle-membrane fusion. as the toxin is highly biologically active, an estimated dose of 1μg/kg body weight is sufficient to induce an insufficient tidal volume and resultant death by asphyxiation. due to its high toxicity, btx antitoxins have been an active area of research. it has been shown that capsaicin (active compound responsible for heat in chili peppers) can bind the trpv1 receptor expressed on cholinergic neurons and inhibit the toxic effects of btx. tetanus toxin tetanus neurotoxin (tent) is a compound that functionally reduces inhibitory transmissions in the nervous system resulting in muscular tetany. tent is similar to btx, and is in fact highly similar in structure and origin; both belonging to the same category of clostridial neurotoxins. like btx, tent inhibits inter-neuron communication by means of vesicular neurotransmitter (nt) release. one notable difference between the two compounds is that while btx inhibits muscular contractions, tent induces them. though both toxins inhibit vesicle release at neuron synapses, the reason for this different manifestation is that btx functions mainly in the peripheral nervous system (pns) while tent is largely active in the central nervous system (cns). this is a result of tent migration through motor neurons to the inhibitory neurons of the spinal cord after entering through endocytosis. this results in a loss of function in inhibitory neurons within the cns resulting in systemic muscular contractions. similar to the prognosis of a lethal dose of btx, tent leads to paralysis and subsequent suffocation. aluminium neurotoxic behavior of aluminium is known to occur upon entry into the circulatory system, where it can migrate to the brain and inhibit some of the crucial functions of the blood brain barrier (bbb). a loss of function in the bbb can produce significant damage to the neurons in the cns, as the barrier protecting the brain from other toxins found in the blood will no longer be capable of such action. though the metal is known to be neurotoxic, effects are usually restricted to patients incapable of removing excess ions from the blood, such as those experiencing renal failure. patients experiencing aluminium toxicity can exhibit symptoms such as impaired learning and reduced motor coordination. additionally, systemic aluminium levels are known to increase with age, and have been shown to correlate with alzheimer's disease, implicating it as a neurotoxic causative compound of the disease. despite its known toxicity in its ionic form, studies are divided on the potential toxicity of using aluminium in packaging and cooking appliances. mercury mercury is capable of inducing cns damage by migrating into the brain by crossing the bbb. mercury exists in a number of different compounds, though methylmercury (mehg+), dimethylmercury and diethylmercury are the only significantly neurotoxic forms. diethylmercury and dimethylmercury are considered some of the most potent neurotoxins ever discovered. mehg+ is usually acquired through consumption of seafood, as it tends to concentrate in organisms high on the food chain. it is known that the mercuric ion inhibits amino acid (aa) and glutamate (glu) transport, potentially leading to excitotoxic effects. anatoxin-a external video very fast death factoruniversity of nottingham anatoxin-a investigations into anatoxin-a, also known as "very fast death factor", began in 1961 following the deaths of cows that drank from a lake containing an algal bloom in saskatchewan, canada. it is a cyanotoxin produced by at least four different genera of cyanobacteria, and has been reported in north america, europe, africa, asia, and new zealand. toxic effects from anatoxin-a progress very rapidly because it acts directly on the nerve cells (neurons). the progressive symptoms of anatoxin-a exposure are loss of coordination, twitching, convulsions and rapid death by respiratory paralysis. the nerve tissues which communicate with muscles contain a receptor called the nicotinic acetylcholine receptor. stimulation of these receptors causes a muscular contraction. the anatoxin-a molecule is shaped so it fits this receptor, and in this way it mimics the natural neurotransmitter normally used by the receptor, acetylcholine. once it has triggered a contraction, anatoxin-a does not allow the neurons to return to their resting state, because it is not degraded by cholinesterase which normally performs this function. as a result, the muscle cells contract permanently, the communication between the brain and the muscles is disrupted and breathing stops. when it was first discovered, the toxin was called the very fast death factor (vfdf) because when it was injected into the body cavity of mice it induced tremors, paralysis and death within a few minutes. in 1977, the structure of vfdf was determined as a secondary, bicyclic amine alkaloid, and it was renamed anatoxin-a. structurally, it is similar to cocaine. there is continued interest in anatoxin-a because of the dangers it presents to recreational and drinking waters, and because it is a particularly useful molecule for investigating acetylcholine receptors in the nervous system. the deadliness of the toxin means that it has a high military potential as a toxin weapon. bungarotoxin bungarotoxin is a compound with known interaction with nicotinic acetylcholine receptors (nachrs), which constitute a family of ion channels whose activity is triggered by neurotransmitter binding. bungarotoxin is produced in a number of different forms, though one of the commonly used forms is the long chain alpha form, α-bungarotoxin, which is isolated from the banded krait snake. though extremely toxic if ingested, α-bungarotoxin has shown extensive usefulness in neuroscience as it is particularly adept at isolating nachrs due to its high affinity to the receptors. as there are multiple forms of bungarotoxin, there are different forms of nachrs to which they will bind, and α-bungarotoxin is particularly specific for α7-nachr. this α7-nachr functions to allow calcium ion influx into cells, and thus when blocked by ingested bungarotoxin will produce damaging effects, as ach signaling will be inhibited. likewise, the use of α-bungarotoxin can be very useful in neuroscience if it is desirable to block calcium flux in order to isolate effects of other channels. additionally, different forms of bungarotoxin may be useful for studying inhibited nachrs and their resultant calcium ion flow in different systems of the body. for example, α-bungarotoxin is specific for nachrs found in the musculature and κ-bungarotoxin is specific for nachrs found in neurons. caramboxin caramboxin caramboxin (cbx) is a toxin found in star fruit (averrhoa carambola). individuals with some types of kidney disease are susceptible to adverse neurological effects including intoxication, seizures and even death after eating star fruit or drinking juice made of this fruit. caramboxin is a new nonpeptide amino acid toxin that stimulate the glutamate receptors in neurons. caramboxin is an agonist of both nmda and ampa glutamatergic ionotropic receptors with potent excitatory, convulsant, and neurodegenerative properties. curare the term "curare" is ambiguous because it has been used to describe a number of poisons which at the time of naming were understood differently from present day understandings. in the past the characterization has meant poisons used by south american tribes on arrows or darts, though it has matured to specify a specific categorization of poisons which act on the neuromuscular junction to inhibit signaling and thus induce muscle relaxation. the neurotoxin category contains a number of distinct poisons, though all were originally purified from plants originating in south america. the effect with which injected curare poison is usually associated is muscle paralysis and resultant death. curare notably functions to inhibit nicotinic acetylcholine receptors at the neuromuscular junction. normally, these receptor channels allow sodium ions into muscle cells to initiate an action potential that leads to muscle contraction. by blocking the receptors, the neurotoxin is capable of significantly reducing neuromuscular junction signaling, an effect which has resulted in its use by anesthesiologists to produce muscular relaxation. ammonia an astrocyte, a cell notable for maintaining the blood brain barrier ammonia toxicity is often seen through two routes of administration, either through consumption or through endogenous ailments such as liver failure. one notable case in which ammonia toxicity is common is in response to cirrhosis of the liver which results in hepatic encephalopathy, and can result in cerebral edema (haussinger 2006). this cerebral edema can be the result of nervous cell remodeling. as a consequence of increased concentrations, ammonia activity in-vivo has been shown to induce swelling of astrocytes in the brain through increased production of cgmp (cyclic guanosine monophosphate) within the cells which leads to protein kinase g-mediated (pkg) cytoskeletal modifications. the resultant effect of this toxicity can be reduced brain energy metabolism and function. importantly, the toxic effects of ammonia on astrocyte remodeling can be reduced through administration of l-carnitine. this astrocyte remodeling appears to be mediated through ammonia-induced mitochondrial permeability transition. this mitochondrial transition is a direct result of glutamine activity a compound which forms from ammonia in-vivo. administration of antioxidants or glutaminase inhibitor can reduce this mitochondrial transition, and potentially also astrocyte remodeling. arsenic arsenic is a neurotoxin commonly found concentrated in areas exposed to agricultural runoff, mining, and smelting sites (martinez-finley 2011). one of the effects of arsenic ingestion during the development of the nervous system is the inhibition of neurite growth which can occur both in pns and the cns. this neurite growth inhibition can often lead to defects in neural migration, and significant morphological changes of neurons during development,) often leading to neural tube defects in neonates. as a metabolite of arsenic, arsenite is formed after ingestion of arsenic and has shown significant toxicity to neurons within about 24 hours of exposure. the mechanism of this cytotoxicity functions through arsenite-induced increases in intracellular calcium ion levels within neurons, which may subsequently reduce mitochondrial transmembrane potential which activates caspases, triggering cell death. another known function of arsenite is its destructive nature towards the cytoskeleton through inhibition of neurofilament transport. this is particularly destructive as neurofilaments are used in basic cell structure and support. lithium administration has shown promise, however, in restoring some of the lost neurofilament motility. additionally, similar to other neurotoxin treatments, the administration of certain antioxidants has shown some promise in reducing neurotoxicity of ingested arsenic. lead lead pipes and solder are common sources of ingested lead. lead is a potent neurotoxin whose toxicity has been recognized for at least thousands of years. though neurotoxic effects for lead are found in both adults and young children, the developing brain is particularly susceptible to lead-induced harm, effects which can include apoptosis and excitotoxicity. an underlying mechanism by which lead is able to cause harm is its ability to be transported by calcium atpase pumps across the bbb, allowing for direct contact with the fragile cells within the central nervous system. neurotoxicity results from lead's ability to act in a similar manner to calcium ions, as concentrated lead will lead to cellular uptake of calcium which disrupts cellular homeostasis and induces apoptosis. it is this intracellular calcium increase that activates protein kinase c (pkc), which manifests as learning deficits in children as a result of early lead