Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). It has been suggested that the apoptotic pathway may plays an important role in dopaminergic neuron death in the SNpc. A new study by researchers from Chinese Academy of Sciences revealed that acetylcholinesterase (AChE) plays an important role during apoptosis of dopaminergic neurons in the neurotoxin model of Parkinson’s desease.
Researchers led by Dr. ZHANG Xuejun from Shanghai Institute of Biochemistry and Cell Biology, CAS found that the increased expression of AChE can induce apoptosis in a number of cell lines and have been working on the role of AChE in the apoptosis pathway for many years. As the expression of AChE increases in apoptotic cells, and the apoptosis pathway is proposed to have an important role in SNpc dopaminergic neuron death, they decided to study the function of AChE in the degeneration of SNpc dopaminergic neurons through apoptosis.
First, they demonstrated the expression of AChE increases in the PD cell model induced by MPP+, and the genetic or pharmacological inhibition of AChE can protect PC12 cells from apoptotic cell death in vitro. They subsequently utilized AChE-deficient mice to establish a mouse model of PD. Reduced dopaminergic neuron loss and lower apoptotic protein expression levels were found in MPTP-treated heterozygous (AChE+/-) mice, compared with MPTP-treated wild type (AChE+/+) mice.
These results provide new insight into the pathological mechanism of PD, and may provide clues for effective PD therapy in clinical practice.
This study entitled “Acetylcholinesterase deficiency decreases apoptosis in dopaminergic neurons in the neurotoxin model of Parkinson’s disease” was published online in International Journal of Biochemistry and Cell Biology on December 21st, 2012. This study was funded by grants from the National Natural Science Foundation of China.
AUTHOR CONTACT:
ZHANG Xuejun
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
Phone: 86-21-54921403;
E-mail: xjzhang@sibcb.ac.cn
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