Neuropathy target esterase (NTE): overview and future

Monocrotophos in Gandaman village: India school lunch deaths and need for improved toxicity testing

“…To the best of our present medical knowledge, monocrotophos is not devoid of this long-term organophosphate toxicity, but reports are more sketchy (e.g., Singh et al 2004). Note also that animal testing is not a reliable predictor for the risk of this type of toxicity in humans, as shown, for example, for organophosphate-related carbamate compounds (Richardson et al 2013). Thus, when it comes to protect the legal rights of victims and their families, our present medical knowledge in this field is not good enough.…”

“…Yet, one should worry that such statements will deprive victims of compensation and medical care for long-term consequences of organophosphate poisoning. Such long-term toxicity includes organophosphateinduced delayed polyneuropathy (Richardson et al 2013) and chronic organophosphate-induced neuropsychiatric disorder (Jokanovic and Kosanovic 2010). It is important to consider that long-term toxicity of organophosphates may occur in the absence of a documented acute intoxication and that such cases might be much more frequent than the fatal acute intoxications, whose tragedy attracts most attention.…”

Hypermethylation reduces the expression of PNPLA7 in hepatocellular carcinoma

“…PNPLA7 is 61% identical to PNPLA6 in amino acid sequence and has the same domain structure, however, it cannot substitute for PNPLA6 during embryonic development (10,12) and it has a different tissue distribution, richest in lysosome, mitochondrion, nucleus and vacuole, and was regulated by insulin and glucose levels (16,17). Both these proteins are predicted to be regulated by cyclic nucleotide as integral membrane proteins and potent …”

Assessment of Enzyme Inhibition: A Review with Examples from the Development of Monoamine Oxidase and Cholinesterase Inhibitory Drugs<strong> </strong>

“…The iPLA2s or patatin-like phospholipases (PNPLAs) are intracellular enzymes that, and contain lipase (GXSXG) and nucleotide-binding (GXGXXG) consensus sequences. The mechanisms involved remain somewhat unclear but it appears that an 'ageing' process may be involved in their inhibition, and that the effects may be owing to a change of iPLA2 function rather that simple inhibition of the esterase activity [107,108]. The organophosphate (OP) 'nerve gases', such as DFP, Sarin, Soman, Tabum and VX, which were originally developed as chemical warfare agents, behave as 'suicide substrates', operating according to the pathway shown in Figure 3.…”

“…The iPLA2s or patatin-like phospholipases (PNPLAs) are intracellular enzymes that, and contain lipase (GXSXG) and nucleotide-binding (GXGXXG) consensus sequences. The mechanisms involved remain somewhat unclear but it appears that an 'ageing' process may be involved in their inhibition, and that the effects may be owing to a change of iPLA2 function rather that simple inhibition of the esterase activity [107,108]. Despite the toxicity, the organophosphate DFP and has been used in the therapy of glaucoma and myasthenia gravis [ [109] and DFP and trichlorfon (metrifonate) has been used in AD therapy [110] and in the treatment of schistosomiasis [111].…”