L15 Cellular Models of Neurotoxicity pt2 Flashcards
What toxin is used commonly in neurotoxicity end point assays?
Organophosphoates (OP).
They exert acute or chronic toxicity.
How does OP elicit acute toxicity?
Via inhibition of acetyl cholinesterase. Results in cholinergic crisis.
What are the known changes in OP-induced delayed neurotoxicity? (OPIDN)
Inhibition and aging of neuropathy target esterase (NTE).
Disruption of cytoskeletal arrasys and protein phosphorylation.
Disruption of Ca2+ homeostasis, upreg of Ca2+ activated enzymes e.g. calpain and transglutaminase.
Which type of toxicity are nerves with long axons more vulnerable to?
Delayed, OPIDN.
e.g. peripheral NS
Name the most commonly used OP in neurotoxicity assay
TCP isomers
What are the two targets of OPs?
Neuropathy target esterase (NTE) and acetyl cholinesterases (AChE).
If target is NTE, aging occurs and OPIDN is induced.
If target is AChE, acute toxicity.
Targets of one type tend to be weaker against other types.
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