Neurotoxic protein

De, P., Dasgupta, S.C., Gomes, A. (2002). A lethal neurotoxic protein from Indian king cobra (Ophiophagus hannah) venom. Indian J. Exp. Biol., 40(12), 1359-1364. 

The section on pharmacology includes the topics of cations, hyperosmolality, adverse reactions and toxicity, toxic effects on red blood cells, cardiovascular effects, nephrotoxicity, neurotoxicity, protein binding, histamine release, pharmacokinetics, formulation, excretion, and biotransformation. 

The botulinum neurotoxins (BoNTs) comprise a family of seven distinct neurotoxic proteins (A-G) produced by immunologically discrete strains of the anaerobic bacterium Clostridium botulinum and in rare cases by Clostridium baratii and Clostridium butyricum (Habermann and Dreyer, 1986 Harvey et ah, 2002 Simpson, 2004). These toxins act on peripheral cholinergic synapses to inhibit spontaneous and impulse-dependent release of acetylcholine (ACh) (Brooks, 1956 Kao et al., 1976). Intoxication by BoNT results in muscle weakness, which can be fatal when the diaphragm and intercostal muscles become sufficiently compromised to impair ventilation (Dickson and Shevky, 1923). The BoNTs are the most potent substances in nature, and exposure to as httle as 1-3 ng/kg may be sufficient to cause human lethahty (GUI, 1982 Middlebrook and Franz, 1997 Amon et al., 2001). 

Two intriguing activities of PrP emerged from studies with transgenic mice expressing mutants lacking the internal hydrophobic domain (HD). First, deleting residues 105-125 from the HD was sufficient to convert PrP from a stress-protective into a neurotoxic protein [52]. Second, co-expression of wild-type PrPc completely blocked the toxic activities of PrPAHD mutants [48, 51, 52] (Fig. 1). The toxic activity of PrPAHD mutants could be related to that of Doppel, a neurotoxic protein with a tertiary structure similar to that of the C-terminal domain of PrPc [140]. Notably, Doppel-induced neurodegeneration is also rescued by the co-expression of PrPc [141-144]. A comprehensive review of Doppel is provided by David West-away in this book. 

The haemolytic and neurotoxic protein isolated from Suberites domuncula, a silicaceous sponge. Lethal in dogs at 10 mg/kg. Non-toxic by mouth. Effects vomiting, diarrhoea, dyspnoea, haemorrhages into gut, peritoneum and pericardium. 

The botulinum neurotoxins (BoNTs) comprise a family of seven distinct neurotoxic proteins (A-G) produced by immunologically discrete strains of the anaerobic bacterium, Clostridium botulinumThese toxins act on peripheral cholinergic... 

Horseshoe crabs use defense tactics in reproduction. They, like other organisms, take in some chemicals with their diet but the status of bioactive metabolites is not known. Also daddy longlegs have chemical defense using a lot of chemical compounds, including alkaloids. Scorpion biotoxins (e.g., bot-ulinum) are the most toxic compounds known. They effect neuromuscular paralytic effects. Botulinum is a neurotoxic protein, very dangerous. Scorpions probably also have alkaloids, although their role is yet to be researched. 

Crowet JM, Lins L, I3upiereux I, et al. Tilted properties of the 67-78 fragment of alpha-synuclein are responsible for membrane destabUization and neurotoxicity. Proteins. 2007 68(4) 936-947. 

Some polymyxins are sold for second-line systemic therapy. Polymyxin B sulfate and colistimethate sodium can be used for intravenous, intramuscular, or intrathecal administration, especially for Pseudomonas aerupinosa mP QXiosis, but also for most other gram-negative organisms, such as those resistant to first-line antibiotics. Nephrotoxicity and various neurotoxicities are common in parenteral, but not in topical, use. Resistance to polymyxins develops slowly, involves mutation and, at least in some bacteria, adaptation, a poorly understood type of resistance that is rapidly lost on transfer to a medium free of polymyxin. Resistance can involve changes in the proteins, the lipopolysaccharides, and lipids of the outer membrane of the cell (52). Polymyxin and colistin show complete cross-resistance. 

Vinca alkaloids are derived from the Madagascar periwinkle plant, Catharanthus roseus. The main alkaloids are vincristine, vinblastine and vindesine. Vinca alkaloids are cell-cycle-specific agents and block cells in mitosis. This cellular activity is due to their ability to bind specifically to tubulin and to block the ability of the protein to polymerize into microtubules. This prevents spindle formation in mitosing cells and causes arrest at metaphase. Vinca alkaloids also inhibit other cellular activities that involve microtubules, such as leukocyte phagocytosis and chemotaxis as well as axonal transport in neurons. Side effects of the vinca alkaloids such as their neurotoxicity may be due to disruption of these functions. 

Dreyer EB, Kaiser PK, Offermann JT, Lipton SA (1990) HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists. Science 248(4953) 364-367 Dreyer EB, Zurakowski D, Gorla M, Vorwerk CK, Lipton SA (1999) The contribution of various NOS gene products to HlV-1 coat protein (gpl20)-mediated retinal ganglion cell injury. Invest Ophthalmol Vis Sci 40(5) 983-989... 

Nath A, Haughey NJ, Jones M, Anderson C, Bell JE, Geiger JD (2000) Synergistic neurotoxicity by human immunodeficiency virus proteins Tat and gpl20 protection by memantine. Ann Neurol 47(2) 186-194... 

The mechanisms of HIV-associated DSP are incompletely understood. Over the years, various hypotheses have been put forward, but recent data suggest that multiple mechanisms are likely to play a role in neuronal or axonal injury in DSP. These processes may be mediated by direct neurotoxicity of HIV or secreted viral proteins such as the envelope glycoprotein gpl20, or by indirect mechanisms... 

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