Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration
| العنوان: | Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration |
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| المؤلفون: | Walter E. Müller, Javier Fernández-Ruiz, Suzana Gispert, Marina Jendrach, Alexei P. Kudin, Annabelle Zimmermann, Andreas S. Reichert, Filomena Ricciardi, Georg Auburger, Udo Rüb, Amy Chen, Jochen Roeper, Leslie Huber, Wolfram S. Kunz, Hermann Rohrer, Robert L. Nussbaum, Hans-Hermann Hoepken, Wolfgang Voos, Miguel Barrera, Dirk Wenzel, Moisés García-Arencibia, Kristina Leuner, Dorothea Becker, Alexander Kurz, Mekhman Azizov |
| المساهمون: | Okazawa, Hitoshi |
| المصدر: | PloS one, vol 4, iss 6 PLoS ONE, Vol 4, Iss 6, p e5777 (2009) PLoS ONE |
| بيانات النشر: | eScholarship, University of California, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Male, Pathology, Aging, Biochemistry/Membrane Proteins and Energy Transduction, Mitochondrion, Neurodegenerative, Transgenic, chemistry.chemical_compound, Mice, Adenosine Triphosphate, Biochemistry/Cell Signaling and Trafficking Structures, 2.1 Biological and endogenous factors, Aetiology, Neurological Disorders/Movement Disorders, Neurons, Multidisciplinary, Parkinson's Disease, biology, Kinase, Dopaminergic, Neurodegeneration, Parkinson Disease, Neurodegenerative Diseases, Cell Biology/Cellular Death and Stress Responses, Mitochondria, Genetics and Genomics/Gene Function, Phenotype, Neurological, alpha-Synuclein, Medicine, Female, Drosophila melanogaster, Neuroscience/Neurobiology of Disease and Regeneration, Research Article, medicine.drug, medicine.medical_specialty, General Science & Technology, Science, Mice, Transgenic, PINK1, Dopamine, Internal medicine, medicine, Animals, ddc:610, Alpha-synuclein, Animal, Neurosciences, biology.organism_classification, medicine.disease, Brain Disorders, Disease Models, Animal, Endocrinology, Genetics and Genomics/Disease Models, chemistry, Gene Expression Regulation, Cell Biology/Neuronal and Glial Cell Biology, Disease Models, Protein Kinases |
| الوصف: | BackgroundParkinson's disease (PD) is an adult-onset movement disorder of largely unknown etiology. We have previously shown that loss-of-function mutations of the mitochondrial protein kinase PINK1 (PTEN induced putative kinase 1) cause the recessive PARK6 variant of PD.Methodology/principal findingsNow we generated a PINK1 deficient mouse and observed several novel phenotypes: A progressive reduction of weight and of locomotor activity selectively for spontaneous movements occurred at old age. As in PD, abnormal dopamine levels in the aged nigrostriatal projection accompanied the reduced movements. Possibly in line with the PARK6 syndrome but in contrast to sporadic PD, a reduced lifespan, dysfunction of brainstem and sympathetic nerves, visible aggregates of alpha-synuclein within Lewy bodies or nigrostriatal neurodegeneration were not present in aged PINK1-deficient mice. However, we demonstrate PINK1 mutant mice to exhibit a progressive reduction in mitochondrial preprotein import correlating with defects of core mitochondrial functions like ATP-generation and respiration. In contrast to the strong effect of PINK1 on mitochondrial dynamics in Drosophila melanogaster and in spite of reduced expression of fission factor Mtp18, we show reduced fission and increased aggregation of mitochondria only under stress in PINK1-deficient mouse neurons.ConclusionThus, aging Pink1(-/-) mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death. |
| وصف الملف: | application/pdf |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::611713730c4a02690e05bbad2d47f6d9Test https://escholarship.org/uc/item/38t6k0psTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....611713730c4a02690e05bbad2d47f6d9 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |