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Does uncoupling protein 2 expression qualify as marker of disease status in LRRK2-associated Parkinson's disease?
Grünewald, Anne; Arns, Bjorn; Meier, Britta et al.
2014In Antioxidants & redox signaling, 20 (13), p. 1955-60
Peer reviewed
 

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Keywords :
Adult; Aged; Biomarkers; Female; Gene Expression Profiling; Humans; Ion Channels/genetics; Male; Middle Aged; Mitochondrial Proteins/genetics; Oxidative Stress/genetics; Parkinson Disease/genetics; Protein-Serine-Threonine Kinases/genetics; RNA, Messenger/genetics; Real-Time Polymerase Chain Reaction
Abstract :
[en] Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common known genetic cause of late-onset Parkinson's disease (PD). However, the penetrance of the disease is below 50% at 60 years of age. LRRK2 is associated with the mitochondrial membrane, and mutant forms impair the function of the organelle and autophagosome clearance in human cells, including induced pluripotent stem cell-derived neurons. Elevated expression of uncoupling proteins has been identified as the cause of mitochondrial depolarization in human fibroblasts with G2019S LRRK2. To identify factors that contribute to the penetrance of LRRK2 mutations, we studied respiratory chain function, markers of mitochondrial uncoupling, oxidative stress, and autophagy in fibroblasts from affected and unaffected carriers of the G2019S mutation. Independent of disease status, all mutation carriers showed reduced mitochondrial membrane potential, increased proton leakage, and more fragmented mitochondria. However, a significant increase in the expression of uncoupling protein 2 (UCP2) was only detected in affected individuals with the G2019S mutation in LRRK2. Since oxidative stress and autophagic markers were selectively increased in some of the PD patients, we hypothesize that UCP2 expression is upregulated in response to elevated reactive oxygen species generation in affected mutation carriers and that UCP2 mRNA levels might, therefore, serve as markers of disease status in LRRK2-associated PD.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Grünewald, Anne   
Arns, Bjorn 
Meier, Britta
Brockmann, Kathrin
Tadic, Vera
Klein, Christine 
 These authors have contributed equally to this work.
External co-authors :
yes
Language :
English
Title :
Does uncoupling protein 2 expression qualify as marker of disease status in LRRK2-associated Parkinson's disease?
Publication date :
2014
Journal title :
Antioxidants & redox signaling
ISSN :
1523-0864
eISSN :
1557-7716
Volume :
20
Issue :
13
Pages :
1955-60
Peer reviewed :
Peer reviewed
Available on ORBilu :
since 09 February 2016

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