DNA damage preceding dopamine neuron degeneration in A53T human α-synuclein transgenic mice.
Defective DNA repair has been linked with age-associated neurodegenerative disorders. Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by genetic and environmental factors. Whether damages to nuclear DNA contribute to neurodegeneration of PD still remain obscure. in this study we aim to explore whether nuclear DNA damage induce dopamine neuron degeneration in A53T human α-Synuclein over expressed mouse model. We investigated the effects of X-ray irradiation on A53T-α-Syn MEFs and A53T-α-Syn transgene mice. Our results indicate that A53T-α-Syn MEFs show a prolonged DNA damage repair process and senescense phenotype. DNA damage preceded onset of motor phenotype in A53T-α-Syn transgenic mice and decrease the number of nigrostriatal dopaminergic neurons. Neurons of A53T-α-Syn transgenic mice are more fragile to DNA damages.
Department of Anatomy and Histology, Lanzhou University, School of Basic Medical Sciences, Lanzhou, China. Electronic address: wangdegui@lzu.edu.cn.
Degui
D
Wang
Department of Anatomy and Histology, Lanzhou University, School of Basic Medical Sciences, Lanzhou, China.
Tianyu
T
Yu
Department of Anatomy and Histology, Lanzhou University, School of Basic Medical Sciences, Lanzhou, China.
Yongqiang
Y
Liu
Department of Anatomy and Histology, Lanzhou University, School of Basic Medical Sciences, Lanzhou, China.
Jun
J
Yan
Department of Anatomy and Histology, Lanzhou University, School of Basic Medical Sciences, Lanzhou, China.
Yingli
Y
Guo
Department of Anatomy and Histology, Lanzhou University, School of Basic Medical Sciences, Lanzhou, China.
Yuhong
Y
Jing
Department of Anatomy and Histology, Lanzhou University, School of Basic Medical Sciences, Lanzhou, China.
Xuguang
X
Yang
Department of Anatomy and Histology, Lanzhou University, School of Basic Medical Sciences, Lanzhou, China. Electronic address: songyanfeng@lzu.edu.cn.
Yanfeng
Y
Song
Department of Internal Medicine, Gansu Academic Institute for Medical Research, Lanzhou, China. Electronic address: tianyxlz@163.com.
Yingxia
Y
Tian
D000818:Animals; D002460:Cell Line; D004249:DNA Damage / Q000235:genetics*; D059290:Dopaminergic Neurons; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000235:genetics* / Q000473:pathology*; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology; D051844:alpha-Synuclein / Q000235:genetics*
D051844:alpha-Synuclein
DNA damage; Mouse; Neurodegeneration; Parkinson's disease; α-Synuclein