ArticleHuman molecular genetics2012
parkin-induced defects in neurophysiology and locomotion are generated by metabolic dysfunction and not oxidative stress.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Diabetes and risk of Parkinson's disease: an updated meta-analysis of case-control studies.PloS one · 2014Pooled it
- Inflammatory cytokine upd3 induces axon length-dependent synapse removal by glia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Folic Acid Improves Parkin-NullAntioxidants (Basel, Switzerland) · 2022Article
- Cross-species models of attention-deficit/hyperactivity disorder and autism spectrum disorder: lessons from CNTNAP2, ADGRL3, and PARK2.Psychiatric genetics · 2019Review
- Drosophila Ubiquitin C-Terminal Hydrolase Knockdown Model of Parkinson's Disease.Scientific reports · 2018Article
- Neonatal C57BL/6J and parkin mice respond differently following developmental manganese exposure: Result of a high dose pilot study.Neurotoxicology · 2018Article
- Linking Glycation and Glycosylation With Inflammation and Mitochondrial Dysfunction in Parkinson's Disease.Frontiers in neuroscience · 2018Review
- Iron Sulfur and Molybdenum Cofactor Enzymes Regulate theFrontiers in physiology · 2018Article
- On the Relationship between Energy Metabolism, Proteostasis, Aging and Parkinson's Disease: Possible Causative Role of Methylglyoxal and Alleviative Potential of Carnosine.Aging and disease · 2017Review
- Mild MPPScientific reports · 2017Article
- The HECT Family Ubiquitin Ligase EEL-1 Regulates Neuronal Function and Development.Cell reports · 2017Article
- Measurement of Carbon Dioxide Production from Radiolabeled Substrates in Drosophila melanogaster.Journal of visualized experiments : JoVE · 2016Article
- Drosophila clueless is involved in Parkin-dependent mitophagy by promoting VCP-mediated Marf degradation.Human molecular genetics · 2016Article
- Article
- A rise in NAD precursor nicotinamide mononucleotide (NMN) after injury promotes axon degeneration.Cell death and differentiation · 2015Article
- Article
- Neurophysiology of Drosophila models of Parkinson's disease.Parkinson's disease · 2015Review
- Abnormal visual gain control in a Parkinson's disease model.Human molecular genetics · 2014Article
- HSP72 is a mitochondrial stress sensor critical for Parkin action, oxidative metabolism, and insulin sensitivity in skeletal muscle.Diabetes · 2014Article
- Parkin reverses TDP-43-induced cell death and failure of amino acid homeostasis.Journal of neurochemistry · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Parkinson's disease (PD) is characterized by movement disorders, including bradykinesia. Analysis of inherited, juvenile PD, identified several genes linked via a common pathway to mitochondrial dysfunction. In this study, we demonstrate that the larva of the Drosophila parkin mutant faithfully models the locomotory and metabolic defects of PD and is an excellent system for investigating their inter-relationship. parkin larvae displayed a marked bradykinesia that was caused by a reduction in both the frequency of peristalsis and speed of muscle contractions. Rescue experiments confirmed that this phenotype was due to a defect in the nervous system and not in the muscle. Furthermore, recordings of motoneuron activity in parkin larvae revealed reduced bursting and a striking reduction in evoked and miniature excitatory junction potentials, suggesting a neuronal deficit. This was supported by our observations in parkin larvae that the resting potential was depolarized, oxygen consumption and ATP concentration were drastically reduced while lactate was increased. These findings suggest that neuronal mitochondrial respiration is severely compromised and there is a compensatory switch to glycolysis for energy production. parkin mutants also possessed overgrown neuromuscular synapses, indicative of oxidative stress, which could be rescued by overexpression of parkin or scavengers of reactive oxygen species (ROS). Surprisingly, scavengers of ROS did not rescue the resting membrane potential and locomotory phenotypes. We therefore propose that mitochondrial dysfunction in parkin mutants induces Parkinsonian bradykinesia via a neuronal energy deficit and resulting synaptic failure, rather than as a consequence of downstream oxidative stress.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.