Neurotoxicity molecular targets

DEF is a relatively weak inhibitor of acetylcholinesterase. The compound is hydrolyzed to a large extent in the intestine to -butyl mercaptan, which is responsible for the late acute effects of DEF. The putative molecular target in neural tissue for initiation of delayed neuropathy is neurotoxic esterase or neuropathy target esterase (NTE). 

Because of the selective injury to the axon by y-diketones and the known importance of microtubules to axonal structure and function, this cytoskeletal element was considered as a molecular target for y-dike tone neurotoxicity. Because the Sertoli cell has axon-like characteristics (33), tubulin was considered an attractive molecular target in testicular injury as well. 

The evidence indicates that although there is a correlation between AChE inhibition and the prevalence and/or severity of OP neurotoxicity, the spectrum of toxic effects elicited by any given OP cannot be attributed entirely to the inhibition of AChE. If this is true, then OPs must react not only with AChE but also with other proteins, and it has been suggested that different OPs elicit different toxicological profiles because each interacts with a unique subset of molecular targets (Chiappa et al., 1995 Liu et ai. 1999 Ray and Richards, 2001). In support of the hypothesis that OPs interact with proteins other than AChE, various OP... 

IV, INTRACELLULAR SIGNALS AND OTHER MOLECULAR TARGETS OF NEUROTOXICITY... 

In addition to these effects, neurotoxic effects of certain PAs have been demonstrated in in-vitro receptor assays [130]. However, the relevance of these rather sporadic effects in vivo needs clarification. In a broad screening in which the interaction of many compounds from different classes of alkaloids with various molecular targets were tested, in almost all cases PAs were found to be inactive [131]. There are a few reports that indicate sporadic and weak (i.e., EC5o>0.5 mg ml antibacterial and antifungal activity [132-134] of PAs. These effects do not indicate an efficient antimicrobial potential of PAs. In this context it should be recalled that in plants PAs are constitutively formed they seem not to be induced by wounding, herbivorous or microbial attack [135-137]. 

J.A. Benson, Toxins and Receptors leads and target sites , in Neurotox 91 Molecular Basis of Drug and Pesticide Action , ed. I. A. Duce, Elsevier Applied Science, London, 1991, pp 57-70. 

In the cases in which human aluminum toxicity has occurred, the target organs appear to be the lung, bone, and the central nervous system. No specific molecular mechanisms have been elucidated for human toxicity to aluminum. In animal models, aluminum can also produce lung, bone, and neurotoxicity, as well as developmental effects in offspring. 

HATHWAY, D.E. (1984) Molecular Aspects of Toxicology (Royal Society of Chemistry London). JOHNSON, M.K. (1982) The target for initiation of delayed neurotoxicity by organophosphorus esters Biochemical studies and toxicological applications. In Reviews of Biochemical Toxicology,... 

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