title: Altered expression of DJ-1 and PINK1 in sporadic ALS and in the SOD1(G93A) ALS mouse model.
abstract: Mitochondrial dysfunction is an important mechanism in the pathogenesis of neurodegenerative diseases such as Parkinson disease and amyotrophic lateral sclerosis (ALS). DJ-1 and PTEN-induced putative kinase 1 (PINK1) are important proteins for the maintenance of mitochondrial function and protection against cell death. Mutations in the genes coding for these proteins cause familial forms of Parkinson disease. Recent studies have postulated that changes in the expression of both proteins are also involved in pathologic mechanisms in ALS mouse models. Here, we studied the mRNA and protein expression of PINK1 and DJ-1 in postmortem brain and spinal cord tissue and muscle biopsy samples from ALS patients and controls and in brain, spinal cord, and gastrocnemius muscle of SOD1(G93A) ALS mice at different disease stages. We found significant decreases of PINK1 and DJ-1 mRNA levels in muscle tissue of SOD1(G93A) mice. Together with the significant decrease of PINK1 mRNA levels in human ALS muscle tissue, statistically nonsignificant reduction of DJ-1 mRNA levels, and reduced immunostaining for PINK1 in human ALS muscle, the results suggest potential pathophysiologic roles for these proteins in both mutant SOD1 transgenic mice and in sporadic ALS(G93A).
authors.affiliation: From the Department of Neurology, Hannover Medical School (SK, JS, NT-H, SK, KJR, RD, SP); and Center for Systems Neuroscience (RD, SP), Hannover, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Knippenberg
authors.forename: Julia
authors.initials: J
authors.lastname: Sipos
authors.forename: Nadine
authors.initials: N
authors.lastname: Thau-Habermann
authors.forename: Sonja
authors.initials: S
authors.lastname: Körner
authors.forename: Klaus Jan
authors.initials: KJ
authors.lastname: Rath
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dengler
authors.forename: Susanne
authors.initials: S
authors.lastname: Petri
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D000099202:PTEN-Induced Putative Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099202:PTEN-Induced Putative Kinase; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; C105131:PARK7 protein, human