Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/43009
Título: Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration
Autores/as: Gispert, Suzana
Ricciardi, Filomena
Kurz, Alexander
Azizov, Mekhman
Hoepken, Hans Hermann
Becker, Dorothea
Voos, Wolfgang
Leuner, Kristina
Müller, Walter E.
Kudin, Alexei P.
Kunz, Wolfram S.
Zimmerman, Annabelle
Roeper, Jochen
Wenzel, Dirk
Jendrach, Marina
Garcia-Arencibia, Moises 
Fernández-Ruiz, Javier
Huber, Leslie
Rohrer, Hermann
Barrera, Miguel
Reichert, Andreas S.
Rüb, Udo
Chen, Amy
Nussbaum, Robert L.
Auburger, Georg
Clasificación UNESCO: 320507 Neurología
Fecha de publicación: 2009
Publicación seriada: PLoS ONE 
Resumen: Background 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. Methodology/Principal Findings 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 α-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. Conclusion Thus, aging Pink1−/− mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death.
URI: http://hdl.handle.net/10553/43009
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0005777
WOS:000266624300013
Fuente: Plos One [ISSN 1932-6203], v. 4 (6)
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