Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity).[3] Neurotoxins are an extensive class of exogenous chemical neurological insults[4] that can adversely affect function in both developing and mature nervous tissue.[5] The term can also be used to classify endogenous compounds, which, when abnormally contacted, can prove neurologically toxic.[4]Though neurotoxins are often neurologically destructive, their ability to specifically target neural components is important in the study of nervous systems.[6] Common examples of neurotoxins include lead,[7] ethanol (drinking alcohol),[8] glutamate,[9] nitric oxide,[10] botulinum toxin (e.g. Botox),[11] tetanus toxin,[12] and tetrodotoxin.[6] Some substances such as nitric oxide and glutamate are in fact essential for proper function of the body and only exert neurotoxic effects at excessive concentrations.
Neurotoxins inhibit neuron control over ion concentrations across the cell membrane,[6] or communication between neurons across a synapse.[13] Local pathology of neurotoxin exposure often includes neuron excitotoxicity or apoptosis[14] but can also include glial cell damage.[15]Macroscopic manifestations of neurotoxin exposure can include widespread central nervous system damage such as intellectual disability,[5] persistent memory impairments,[16] epilepsy, and dementia.[17] Additionally, neurotoxin-mediated peripheral nervous system damage such as neuropathy or myopathy is common. Support has been shown for a number of treatments aimed at attenuating neurotoxin-mediated injury, such as antioxidant[8] and antitoxin[18] administration.
Additionally, the response of cells to chemicals may not accurately convey a distinction between neurotoxins and cytotoxins, as symptoms like oxidative stress or skeletal modifications may occur in response to either.[26]
- Deshane, Jessy; Garner, Craig C.; Sontheimer, Harald (2003). "Chlorotoxin Inhibits Glioma Cell Invasion via Matrix Metalloproteinase-2". The Journal of Biological Chemistry. 278 (6): 4135–144. doi:10.1074/jbc.m205662200. PMID 12454020.
Potassium channel[edit]
Tetraethylammonium[edit]
Tetraethylammonium (TEA) is a compound that, like a number of neurotoxins, was first identified through its damaging effects to the nervous system and shown to have the capacity of inhibiting the function of motor nerves and thus the contraction of the musculature in a manner similar to that of curare.[53]Additionally, through chronic TEA administration, muscular atrophy would be induced.[53] It was later determined that TEA functions in-vivo primarily through its ability to inhibit both the potassium channels responsible for the delayed rectifier seen in an action potential and some population of calcium-dependent potassium channels.[32] It is this capability to inhibit potassium flux in neurons that has made TEA one of the most important tools in neuroscience. It has been hypothesized that the ability for TEA to inhibit potassium channels is derived from its similar space-filling structure to potassium ions.[53] What makes TEA very useful for neuroscientists is its specific ability to eliminate potassium channel activity, thereby allowing the study of neuron response contributions of other ion channels such as voltage gated sodium channels.[54] In addition to its many uses in neuroscience research, TEA has been shown to perform as an effective treatment of Parkinson's disease through its ability to limit the progression of the disease.[55]
Chloride channel[edit]
Chlorotoxin[edit]
Chlorotoxin (Cltx) is the active compound found in scorpion venom, and is primarily toxic because of its ability to inhibit the conductance of chloride channels.[33] Ingestion of lethal volumes of Cltx results in paralysis through this ion channel disruption. Similar to botulinum toxin, Cltx has been shown to possess significant therapeutic value. Evidence has shown that Cltx can inhibit the ability for gliomas to infiltrate healthy nervous tissue in the brain, significantly reducing the potential invasive harm caused by tumors.[56][57]
Calcium channel[edit]
Conotoxin[edit]
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.[58][59] 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.[58] 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.[60] 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.[61]
Cytoskeleton interference[edit]
Arsenic[edit]
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[88] which can occur both in PNS and the CNS.[89] This neurite growth inhibition can often lead to defects in neural migration, and significant morphological changes of neurons during development,[90]) often leading to neural tube defects in neonates.[91] 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.[90] Another known function of arsenite is its destructive nature towards the cytoskeleton through inhibition of neurofilamenttransport.[42] 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.[92] Additionally, similar to other neurotoxin treatments, the administration of certain antioxidants has shown some promise in reducing neurotoxicity of ingested arsenic.[90]
Ammonia[edit]
Ammonia toxicity is often seen through two routes of administration, either through consumption or through endogenous ailments such as liver failure.[93][94] 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.[43] 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.[93] 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.[95] Administration of antioxidants or glutaminase inhibitor can reduce this mitochondrial transition, and potentially also astrocyte remodeling.[95]
MPP+, the toxic metabolite of MPTP is a selective neurotoxin which interferes with oxidative phosphorylation in mitochondria by inhibiting complex I, leading to the depletion of ATP and subsequent cell death. This occurs almost exclusively in dopaminergic neurons of the substantia nigra, resulting in the presentation of permanent parkinsonism in exposed subjects 2–3 days after administration.
https://en.wikipedia.org/wiki/Neurotoxin
| Animal | |
|---|---|
| Bacterial | |
| Cyanotoxins | |
| Plant | |
| Mycotoxins | |
| Pesticides | |
| Nerve agents | |
| Bicyclic phosphates | |
| Other | |
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