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Int J Biochem Cell Biol. 2013 Feb;45(2):265-72. doi: 10.1016/j.biocel.2012.11.015. Epub 2012 Nov 29.

Acetylcholinesterase deficiency decreases apoptosis in dopaminergic neurons in the neurotoxin model of Parkinson's disease.

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1
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of Chinese Academy of Sciences, 320 YueYang Road, Shanghai 200031, PR China.

Abstract

The apoptosis pathway has been proposed to be involved in causing neuronal cell death in the pathogenesis of Parkinson's disease. However, the details of this pathway are poorly understood. Previous research has shown increased acetylcholinesterase expression during apoptosis in various cell types, which suggests that acetylcholinesterase has a potential role in neuronal cell death. In this study, we found that acetylcholinesterase protein expression increased and caspase-3 was activated in PC12 cells treated with 1-methyl-4-phenylpyridinium. Furthermore, the genetic or pharmacological inhibition of acetylcholinesterase was shown to protect PC12 cells from MPP+ induced apoptotic cell death. To study the function of acetylcholinesterase as a mechanism of neuronal cell death in vivo, we subsequently established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Parkinson's disease mouse model utilizing acetylcholinesterase-deficient mice. Studies in these mice revealed reduced dopaminergic neuron loss and lower expression levels of apoptotic proteins in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated heterozygous mice compared to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated wild-type mice. We conclude that it is highly probable that acetylcholinesterase is involved in the pathogenesis of the neurotoxin model of Parkinson's disease via apoptosis. Specifically, a deficiency or inhibition of acetylcholinesterase can decrease apoptosis and protect dopaminergic neurons in the neurotoxin model of Parkinson's disease.

PMID:
23201480
DOI:
10.1016/j.biocel.2012.11.015
[Indexed for MEDLINE]
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