title: Induction of parkinsonism-related proteins in the spinal motor neurons of transgenic mouse carrying a mutant SOD1 gene.
abstract: 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.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University, Okayama, Japan. morinobu@cc.okayama-u.ac.jp
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Morimoto
authors.forename: Makiko
authors.initials: M
authors.lastname: Nagai
authors.forename: Kazunori
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohta
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kurata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takehisa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Tohru
authors.initials: T
authors.lastname: Matsuura
authors.forename: Masato
authors.initials: M
authors.lastname: Asanuma
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: 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
chemical_list: 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