Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration.
<h4<Background</h4<Parkinson'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.&l...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Suzana Gispert [verfasserIn] Filomena Ricciardi [verfasserIn] Alexander Kurz [verfasserIn] Mekhman Azizov [verfasserIn] Hans-Hermann Hoepken [verfasserIn] Dorothea Becker [verfasserIn] Wolfgang Voos [verfasserIn] Kristina Leuner [verfasserIn] Walter E Müller [verfasserIn] Alexei P Kudin [verfasserIn] Wolfram S Kunz [verfasserIn] Annabelle Zimmermann [verfasserIn] Jochen Roeper [verfasserIn] Dirk Wenzel [verfasserIn] Marina Jendrach [verfasserIn] Moisés García-Arencíbia [verfasserIn] Javier Fernández-Ruiz [verfasserIn] Leslie Huber [verfasserIn] Hermann Rohrer [verfasserIn] Miguel Barrera [verfasserIn] Andreas S Reichert [verfasserIn] Udo Rüb [verfasserIn] Amy Chen [verfasserIn] Robert L Nussbaum [verfasserIn] Georg Auburger [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2009 |
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| Übergeordnetes Werk: |
In: PLoS ONE - Public Library of Science (PLoS), 2007, 4(2009), 6, p e5777 |
|---|---|
| Übergeordnetes Werk: |
volume:4 ; year:2009 ; number:6, p e5777 |
| Links: |
|---|
| DOI / URN: |
10.1371/journal.pone.0005777 |
|---|
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DOAJ051378825 |
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| 245 | 1 | 0 | |a Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration. |
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| 520 | |a <h4<Background</h4<Parkinson'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.<h4<Methodology/principal findings</h4<Now 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.<h4<Conclusion</h4<Thus, aging Pink1(-/-) mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death. | ||
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| 700 | 0 | |a Hans-Hermann Hoepken |e verfasserin |4 aut | |
| 700 | 0 | |a Dorothea Becker |e verfasserin |4 aut | |
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| 700 | 0 | |a Walter E Müller |e verfasserin |4 aut | |
| 700 | 0 | |a Alexei P Kudin |e verfasserin |4 aut | |
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| 700 | 0 | |a Dirk Wenzel |e verfasserin |4 aut | |
| 700 | 0 | |a Marina Jendrach |e verfasserin |4 aut | |
| 700 | 0 | |a Moisés García-Arencíbia |e verfasserin |4 aut | |
| 700 | 0 | |a Javier Fernández-Ruiz |e verfasserin |4 aut | |
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| 700 | 0 | |a Miguel Barrera |e verfasserin |4 aut | |
| 700 | 0 | |a Andreas S Reichert |e verfasserin |4 aut | |
| 700 | 0 | |a Udo Rüb |e verfasserin |4 aut | |
| 700 | 0 | |a Amy Chen |e verfasserin |4 aut | |
| 700 | 0 | |a Robert L Nussbaum |e verfasserin |4 aut | |
| 700 | 0 | |a Georg Auburger |e verfasserin |4 aut | |
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10.1371/journal.pone.0005777 doi (DE-627)DOAJ051378825 (DE-599)DOAJ45f68ab49b2d403fa1646e411e62f433 DE-627 ger DE-627 rakwb eng Suzana Gispert verfasserin aut Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration. 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4<Parkinson'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.<h4<Methodology/principal findings</h4<Now 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.<h4<Conclusion</h4<Thus, aging Pink1(-/-) mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death. Medicine R Science Q Filomena Ricciardi verfasserin aut Alexander Kurz verfasserin aut Mekhman Azizov verfasserin aut Hans-Hermann Hoepken verfasserin aut Dorothea Becker verfasserin aut Wolfgang Voos verfasserin aut Kristina Leuner verfasserin aut Walter E Müller verfasserin aut Alexei P Kudin verfasserin aut Wolfram S Kunz verfasserin aut Annabelle Zimmermann verfasserin aut Jochen Roeper verfasserin aut Dirk Wenzel verfasserin aut Marina Jendrach verfasserin aut Moisés García-Arencíbia verfasserin aut Javier Fernández-Ruiz verfasserin aut Leslie Huber verfasserin aut Hermann Rohrer verfasserin aut Miguel Barrera verfasserin aut Andreas S Reichert verfasserin aut Udo Rüb verfasserin aut Amy Chen verfasserin aut Robert L Nussbaum verfasserin aut Georg Auburger verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 4(2009), 6, p e5777 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:4 year:2009 number:6, p e5777 https://doi.org/10.1371/journal.pone.0005777 kostenfrei https://doaj.org/article/45f68ab49b2d403fa1646e411e62f433 kostenfrei https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19492057/?tool=EBI kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2009 6, p e5777 |
| spelling |
10.1371/journal.pone.0005777 doi (DE-627)DOAJ051378825 (DE-599)DOAJ45f68ab49b2d403fa1646e411e62f433 DE-627 ger DE-627 rakwb eng Suzana Gispert verfasserin aut Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration. 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4<Parkinson'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.<h4<Methodology/principal findings</h4<Now 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.<h4<Conclusion</h4<Thus, aging Pink1(-/-) mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death. Medicine R Science Q Filomena Ricciardi verfasserin aut Alexander Kurz verfasserin aut Mekhman Azizov verfasserin aut Hans-Hermann Hoepken verfasserin aut Dorothea Becker verfasserin aut Wolfgang Voos verfasserin aut Kristina Leuner verfasserin aut Walter E Müller verfasserin aut Alexei P Kudin verfasserin aut Wolfram S Kunz verfasserin aut Annabelle Zimmermann verfasserin aut Jochen Roeper verfasserin aut Dirk Wenzel verfasserin aut Marina Jendrach verfasserin aut Moisés García-Arencíbia verfasserin aut Javier Fernández-Ruiz verfasserin aut Leslie Huber verfasserin aut Hermann Rohrer verfasserin aut Miguel Barrera verfasserin aut Andreas S Reichert verfasserin aut Udo Rüb verfasserin aut Amy Chen verfasserin aut Robert L Nussbaum verfasserin aut Georg Auburger verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 4(2009), 6, p e5777 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:4 year:2009 number:6, p e5777 https://doi.org/10.1371/journal.pone.0005777 kostenfrei https://doaj.org/article/45f68ab49b2d403fa1646e411e62f433 kostenfrei https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19492057/?tool=EBI kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2009 6, p e5777 |
| allfields_unstemmed |
10.1371/journal.pone.0005777 doi (DE-627)DOAJ051378825 (DE-599)DOAJ45f68ab49b2d403fa1646e411e62f433 DE-627 ger DE-627 rakwb eng Suzana Gispert verfasserin aut Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration. 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4<Parkinson'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.<h4<Methodology/principal findings</h4<Now 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.<h4<Conclusion</h4<Thus, aging Pink1(-/-) mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death. Medicine R Science Q Filomena Ricciardi verfasserin aut Alexander Kurz verfasserin aut Mekhman Azizov verfasserin aut Hans-Hermann Hoepken verfasserin aut Dorothea Becker verfasserin aut Wolfgang Voos verfasserin aut Kristina Leuner verfasserin aut Walter E Müller verfasserin aut Alexei P Kudin verfasserin aut Wolfram S Kunz verfasserin aut Annabelle Zimmermann verfasserin aut Jochen Roeper verfasserin aut Dirk Wenzel verfasserin aut Marina Jendrach verfasserin aut Moisés García-Arencíbia verfasserin aut Javier Fernández-Ruiz verfasserin aut Leslie Huber verfasserin aut Hermann Rohrer verfasserin aut Miguel Barrera verfasserin aut Andreas S Reichert verfasserin aut Udo Rüb verfasserin aut Amy Chen verfasserin aut Robert L Nussbaum verfasserin aut Georg Auburger verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 4(2009), 6, p e5777 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:4 year:2009 number:6, p e5777 https://doi.org/10.1371/journal.pone.0005777 kostenfrei https://doaj.org/article/45f68ab49b2d403fa1646e411e62f433 kostenfrei https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19492057/?tool=EBI kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2009 6, p e5777 |
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10.1371/journal.pone.0005777 doi (DE-627)DOAJ051378825 (DE-599)DOAJ45f68ab49b2d403fa1646e411e62f433 DE-627 ger DE-627 rakwb eng Suzana Gispert verfasserin aut Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration. 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4<Parkinson'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.<h4<Methodology/principal findings</h4<Now 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.<h4<Conclusion</h4<Thus, aging Pink1(-/-) mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death. Medicine R Science Q Filomena Ricciardi verfasserin aut Alexander Kurz verfasserin aut Mekhman Azizov verfasserin aut Hans-Hermann Hoepken verfasserin aut Dorothea Becker verfasserin aut Wolfgang Voos verfasserin aut Kristina Leuner verfasserin aut Walter E Müller verfasserin aut Alexei P Kudin verfasserin aut Wolfram S Kunz verfasserin aut Annabelle Zimmermann verfasserin aut Jochen Roeper verfasserin aut Dirk Wenzel verfasserin aut Marina Jendrach verfasserin aut Moisés García-Arencíbia verfasserin aut Javier Fernández-Ruiz verfasserin aut Leslie Huber verfasserin aut Hermann Rohrer verfasserin aut Miguel Barrera verfasserin aut Andreas S Reichert verfasserin aut Udo Rüb verfasserin aut Amy Chen verfasserin aut Robert L Nussbaum verfasserin aut Georg Auburger verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 4(2009), 6, p e5777 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:4 year:2009 number:6, p e5777 https://doi.org/10.1371/journal.pone.0005777 kostenfrei https://doaj.org/article/45f68ab49b2d403fa1646e411e62f433 kostenfrei https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19492057/?tool=EBI kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2009 6, p e5777 |
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10.1371/journal.pone.0005777 doi (DE-627)DOAJ051378825 (DE-599)DOAJ45f68ab49b2d403fa1646e411e62f433 DE-627 ger DE-627 rakwb eng Suzana Gispert verfasserin aut Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration. 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4<Parkinson'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.<h4<Methodology/principal findings</h4<Now 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.<h4<Conclusion</h4<Thus, aging Pink1(-/-) mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death. Medicine R Science Q Filomena Ricciardi verfasserin aut Alexander Kurz verfasserin aut Mekhman Azizov verfasserin aut Hans-Hermann Hoepken verfasserin aut Dorothea Becker verfasserin aut Wolfgang Voos verfasserin aut Kristina Leuner verfasserin aut Walter E Müller verfasserin aut Alexei P Kudin verfasserin aut Wolfram S Kunz verfasserin aut Annabelle Zimmermann verfasserin aut Jochen Roeper verfasserin aut Dirk Wenzel verfasserin aut Marina Jendrach verfasserin aut Moisés García-Arencíbia verfasserin aut Javier Fernández-Ruiz verfasserin aut Leslie Huber verfasserin aut Hermann Rohrer verfasserin aut Miguel Barrera verfasserin aut Andreas S Reichert verfasserin aut Udo Rüb verfasserin aut Amy Chen verfasserin aut Robert L Nussbaum verfasserin aut Georg Auburger verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 4(2009), 6, p e5777 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:4 year:2009 number:6, p e5777 https://doi.org/10.1371/journal.pone.0005777 kostenfrei https://doaj.org/article/45f68ab49b2d403fa1646e411e62f433 kostenfrei https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19492057/?tool=EBI kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2009 6, p e5777 |
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Suzana Gispert @@aut@@ Filomena Ricciardi @@aut@@ Alexander Kurz @@aut@@ Mekhman Azizov @@aut@@ Hans-Hermann Hoepken @@aut@@ Dorothea Becker @@aut@@ Wolfgang Voos @@aut@@ Kristina Leuner @@aut@@ Walter E Müller @@aut@@ Alexei P Kudin @@aut@@ Wolfram S Kunz @@aut@@ Annabelle Zimmermann @@aut@@ Jochen Roeper @@aut@@ Dirk Wenzel @@aut@@ Marina Jendrach @@aut@@ Moisés García-Arencíbia @@aut@@ Javier Fernández-Ruiz @@aut@@ Leslie Huber @@aut@@ Hermann Rohrer @@aut@@ Miguel Barrera @@aut@@ Andreas S Reichert @@aut@@ Udo Rüb @@aut@@ Amy Chen @@aut@@ Robert L Nussbaum @@aut@@ Georg Auburger @@aut@@ |
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Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration |
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parkinson phenotype in aged pink1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration |
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Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration. |
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<h4<Background</h4<Parkinson'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.<h4<Methodology/principal findings</h4<Now 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.<h4<Conclusion</h4<Thus, aging Pink1(-/-) mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death. |
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<h4<Background</h4<Parkinson'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.<h4<Methodology/principal findings</h4<Now 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.<h4<Conclusion</h4<Thus, aging Pink1(-/-) mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death. |
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<h4<Background</h4<Parkinson'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.<h4<Methodology/principal findings</h4<Now 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.<h4<Conclusion</h4<Thus, aging Pink1(-/-) mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death. |
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7.399658 |