Overexpression of parkin ameliorates dopaminergic neurodegeneration induced by 1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice.
Mutations in the parkin gene are currently thought to be the most common cause of recessive familial Parkinsonism. Parkin functions as an E3 ligase to regulate protein turnover, and its function in mitochondrial quality control has been reported recently. Overexpression of parkin has been found to prevent neuronal degeneration under various conditions both in vivo and in vitro. Here, we generated a transgenic mouse model in which expression of wild type parkin was driven by neuron-specific enolase (NSE) promoter. We reported that both young and old parkin transgenic mice exhibited less reduction of striatal TH protein and number of TH positive neurons in the substantia nigra induced by 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP), compared to wild type littermates. MPTP-induced mitochondrial impairment in the substantia nigra was improved in young parkin transgenic mice. Decreased striatal α-synuclein was demonstrated in old parkin transgenic mice. These results provide reliable evidence from the transgenic mouse model for parkin that overexpression of parkin may attenuate dopaminergic neurodegeneration induced by MPTP through protection of mitochondria and reduction of α-synuclein in the nigrostriatal pathway.
State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai, China.
Minjuan
M
Bian
Jie
J
Liu
Xiaoqi
X
Hong
Mei
M
Yu
Yufang
Y
Huang
Zhejin
Z
Sheng
Jian
J
Fei
Fang
F
Huang
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000235:genetics / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D000071617:Protein Deglycase DJ-1; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism
D015513:Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051844:alpha-Synuclein; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D054464:Peroxiredoxins; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1; D010751:Phosphopyruvate Hydratase; D004298:Dopamine