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DJ-1 is a redox sen...
DJ-1 is a redox sensitive adapter protein for high molecular weight complexes involved in regulation of catecholamine homeostasis
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Piston, Dominik (författare)
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Alvarez-Erviti, Lydia (författare)
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Bansal, Vikas (författare)
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visa fler...
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Gargano, Daniela (författare)
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Yao, Zhi (författare)
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Szabadkai, Gyorgy (författare)
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Odell, Mark (författare)
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Puno, M. Rhyan (författare)
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Björkblom, Benny (författare)
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Maple-Grodem, Jodi (författare)
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Breuer, Peter (författare)
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Kaut, Oliver (författare)
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Larsen, Jan Petter (författare)
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Bonn, Stefan (författare)
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Moller, Simon Geir (författare)
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Wuellner, Ullrich (författare)
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Schapira, Anthony H. V. (författare)
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Gegg, Matthew E. (författare)
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visa färre...
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(utgivare)
- OXFORD UNIV PRESS 2017
- 2017
- Engelska.
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Ingår i: Human Molecular Genetics. - 0964-6906. ; 26:20, 4028-4041
Abstract
Ämnesord
Stäng
- DJ-1 is an oxidation sensitive protein encoded by the PARK7 gene. Mutations in PARK7 are a rare cause of familial recessive Parkinson's disease (PD), but growing evidence suggests involvement of DJ-1 in idiopathic PD. The key clinical features of PD, rigidity and bradykinesia, result from neurotransmitter imbalance, particularly the catecholamines dopamine (DA) and noradrenaline. We report in human brain and human SH-SY5Y neuroblastoma cell lines that DJ-1 predominantly forms high molecular weight (HMW) complexes that included RNA metabolism proteins hnRNPA1 and PABP1 and the glycolysis enzyme GAPDH. In cell culture models the oxidation status of DJ-1 determined the specific complex composition. RNA sequencing indicated that oxidative changes to DJ-1 were concomitant with changes in mRNA transcripts mainly involved in catecholamine metabolism. Importantly, loss of DJ-1 function upon knock down (KD) or expression of the PD associated form L166P resulted in the absence of HMW DJ-1 complexes. In the KD model, the absence of DJ-1 complexes was accompanied by impairment in catecholamine homeostasis, with significant increases in intracellular DA and noraderenaline levels. These changes in catecholamines could be rescued by re-expression of DJ-1. This catecholamine imbalance may contribute to the particular vulnerability of dopaminergic and noradrenergic neurons to neurodegeneration in PARK7-related PD. Notably, oxidised DJ-1 was significantly decreased in idiopathic PD brain, suggesting altered complex function may also play a role in the more common sporadic form of the disease.
Ämnesord
- Medical and Health Sciences (hsv)
- Basic Medicine (hsv)
- Cell and Molecular Biology (hsv)
- Medicin och hälsovetenskap (hsv)
- Medicinska och farmaceutiska grundvetenskaper (hsv)
- Cell- och molekylärbiologi (hsv)
- Medical and Health Sciences (hsv)
- Medical Biotechnology (hsv)
- Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) (hsv)
- Medicin och hälsovetenskap (hsv)
- Medicinsk bioteknologi (hsv)
- Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci) (hsv)
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Till lärosätets databas
- Av författaren/redakt...
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Piston, Dominik
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Alvarez-Erviti, ...
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Bansal, Vikas
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Gargano, Daniela
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Yao, Zhi
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Szabadkai, Gyorg ...
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visa fler...
-
Odell, Mark
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Puno, M. Rhyan
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Björkblom, Benny
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Maple-Grodem, Jo ...
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Breuer, Peter
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Kaut, Oliver
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Larsen, Jan Pett ...
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Bonn, Stefan
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Moller, Simon Ge ...
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Wuellner, Ullric ...
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Schapira, Anthon ...
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Gegg, Matthew E.
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visa färre...
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