2006
DOI: 10.1111/j.1460-9568.2006.04812.x
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Adaptive acetylcholinesterase splicing patterns attenuate 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced Parkinsonism in mice

Abstract: Balanced dopaminergic cholinergic interactions are crucial for proper basal ganglia function. This is dramatically demonstrated by the worsening of Parkinson's disease symptoms following acetylcholinesterase (AChE) inhibition. Typically, in the brain, the synapse-anchored synaptic AChE (AChE-S) variant is prevalent whereas the soluble readthrough AChE (AChE-R) variant is induced in response to cholinesterase inhibition or stress. Because of the known functional differences between these variants and the fact t… Show more

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Cited by 22 publications
(22 citation statements)
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“…In engineered mice, over-expression of AChE-R confers resistance to the dopaminergic and AChE inhibiting neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) with or without co-exposure to organophosphate anti-cholinesterases. In contrast, AChE-S over-expressor mice showed increased susceptibility to MPTP as compared to wildtype FVB/N [13] . Importantly, the difference between these enzyme variants is limited to the C terminus and does not affect their hydrolytic activity [14] .…”
Section: Introductionmentioning
confidence: 77%
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“…In engineered mice, over-expression of AChE-R confers resistance to the dopaminergic and AChE inhibiting neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) with or without co-exposure to organophosphate anti-cholinesterases. In contrast, AChE-S over-expressor mice showed increased susceptibility to MPTP as compared to wildtype FVB/N [13] . Importantly, the difference between these enzyme variants is limited to the C terminus and does not affect their hydrolytic activity [14] .…”
Section: Introductionmentioning
confidence: 77%
“…Transgenic strains and AChE activity measurement were as previously described [13,19,20] . All experiments were carried out in accordance with the Animal Care and Use Committee of the Hebrew University of Jerusalem (approval No.…”
Section: Methodsmentioning
confidence: 99%
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“…In a MPTP mouse model, overexpression of one splice variant of the acetylcholinesterase gene, AChE-R, was protective, whereas overexpression of another variant, AChE-S, enhanced the development of Parkinsonism (Ben-Shaul et al, 2006). In another study, a shift in splice variants from AChE-S to AChE-R was associated with neurodegeneration and stress-associated disorders (Meshorer and Soreq, 2006).…”
Section: Methodsmentioning
confidence: 98%