Induction of parkinsonism-related proteins in the spinal motor neurons of transgenic mouse carrying a mutant SOD1 gene.
Amyotrophic lateral sclerosis is a progressive and fatal disease caused by selective death of motor neurons, and a number of these patients carry mutations in the superoxide dismutase 1 (SOD1) gene involved in ameliorating oxidative stress. Recent studies indicate that oxidative stress and disruption of mitochondrial homeostasis is a common mechanism for motor neuron degeneration in amyotrophic lateral sclerosis and the loss of midbrain dopamine neurons in Parkinson's disease. Therefore, the present study investigated the presence and alterations of familial Parkinson's disease-related proteins, PINK1 and DJ-1, in spinal motor neurons of G93ASOD1 transgenic mouse model of amyotrophic lateral sclerosis. Following onset of disease, PINK1 and DJ-1 protein expression increased in the spinal motor neurons. The activated form of p53 also increased and translocated to the nuclei of spinal motor neurons, followed by increased expression of p53-activated gene 608 (PAG608). This is the first report demonstrating that increased expression of PAG608 correlates with activation of phosphorylated p53 in spinal motor neurons of an amyotrophic lateral sclerosis model. These results provide further evidence of the profound correlations between spinal motor neurons of amyotrophic lateral sclerosis and parkinsonism-related proteins.
Morimoto
Nobutoshi
N
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University, Okayama, Japan. morinobu@cc.okayama-u.ac.jp
Nagai
Makiko
M
Miyazaki
Kazunori
K
Ohta
Yasuyuki
Y
Kurata
Tomoko
T
Takehisa
Yasushi
Y
Ikeda
Yoshio
Y
Matsuura
Tohru
T
Asanuma
Masato
M
Abe
Koji
K
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D013116:Spinal Cord / Q000166:cytology*; D013482:Superoxide Dismutase / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D016601:RNA-Binding Proteins; D013482:Superoxide Dismutase; D016159:Tumor Suppressor Protein p53; D000099202:PTEN-Induced Putative Kinase; C491518:Wig1 protein, mouse; C109415:SOD1 G93A protein; C503466:PARK7 protein, mouse