TY  - JOUR
A1  - Gispert, Suzana
A1  - Ricciardi, Filomena
A1  - Kurz, Alexander
A1  - Azizov, Mekhman
A1  - Hoepken, Hans-Hermann
A1  - Becker, Dorothea
A1  - Voos, Wolfgang
A1  - Leuner, Kristina
A1  - Müller, Walter E.
A1  - Kudin, Alexei P.
A1  - Kunz, Wolfram S.
A1  - Zimmermann, Annabelle
A1  - Roeper, Jochen
A1  - Wenzel, Dirk
A1  - Jendrach, Marina
A1  - García-Arencíbia, Moisés
A1  - Fernández-Ruiz, Javier
A1  - Huber, Leslie
A1  - Rohrer, Hermann
A1  - Barrera, Miguel
A1  - Reichert, Andreas
A1  - Rüb, Udo
A1  - Chen, Amy
A1  - Nussbaum, Robert L.
A1  - Auburger, Georg
T1  - Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration
T2  - PLoS One
N2  - 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 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. Conclusion Thus, aging Pink1 -/- mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death.
Y1  - 2009
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/6722
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-68239
SN  - 1932-6203
N1  - This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
VL  - 4
IS  - (6): e5777
ER  -