ArticleFree radical biology & medicine2014
α-Synuclein and mitochondrial bioenergetics regulate tetrahydrobiopterin levels in a human dopaminergic model of Parkinson disease.
Article in Free radical biology & medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Comparative Proteomics Highlights that GenX Exposure Leads to Metabolic Defects and Inflammation in Astrocytes.Environmental science & technology · 2024Article
- Alpha synuclein post translational modifications: potential targets for Parkinson's disease therapy?Frontiers in molecular neuroscience · 2023Review
- Mitochondrial Phenotypes in Parkinson's Diseases-A Focus on Human iPSC-Derived Dopaminergic Neurons.Cells · 2021Review
- Impairment of Nrf2- and Nitrergic-Mediated Gastrointestinal Motility in an MPTP Mouse Model of Parkinson's Disease.Digestive diseases and sciences · 2019Article
- Modeling Cell-Cell Interactions in Parkinson's Disease Using Human Stem Cell-Based Models.Frontiers in cellular neuroscience · 2019Article
- Neuroinflammation in L-DOPA-induced dyskinesia: beyond the immune function.Journal of neural transmission (Vienna, Austria : 1996) · 2018Review
- Sepiapterin reductase gene-disrupted mice suffer from hypertension with fluctuation and bradycardia.Physiological reports · 2017Article
- 2-Year Natural Decline of Cardiac Sympathetic Innervation in Idiopathic Parkinson Disease Studied with 11C-Hydroxyephedrine PET.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2017Article
- Mitophagy in Parkinson's Disease: Pathogenic and Therapeutic Implications.Frontiers in neurology · 2017Review
- Mitochondrial respiration is sensitive to cytoarchitectural breakdown.Integrative biology : quantitative biosciences from nano to macro · 2016Article
- Protein-protein interaction networks identify targets which rescue the MPP+ cellular model of Parkinson's disease.Scientific reports · 2015Article
- The E3 ubiquitin ligase seven in absentia homolog 1 may be a potential new therapeutic target for Parkinson's disease.Neural regeneration research · 2015Article
- Direct visualization of alpha-synuclein oligomers reveals previously undetected pathology in Parkinson's disease brain.Brain : a journal of neurology · 2015Article
- Parkinson's disease in GTP cyclohydrolase 1 mutation carriers.Brain : a journal of neurology · 2015Article
- Reply: Parkinson's disease in GTP cyclohydrolase 1 mutation carriers.Brain : a journal of neurology · 2015Article
- A requirement for Gch1 and tetrahydrobiopterin in embryonic development.Developmental biology · 2015Article
- Inhibition of calpain prevents manganese-induced cell injury and alpha-synuclein oligomerization in organotypic brain slice cultures.PloS one · 2015Article
- Article
- Genetic deletion of the GATA1-regulated protein α-synuclein reduces oxidative stress and nitric oxide synthase levels in mature erythrocytes.American journal of hematology · 2014Article
- Alteration of striatal tetrahydrobiopterin in iron-induced unilateral model of Parkinson's disease.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2014Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Parkinson disease (PD) is a multifactorial disease resulting in preferential death of the dopaminergic neurons in the substantia nigra. Studies of PD-linked genes and toxin-induced models of PD have implicated mitochondrial dysfunction, oxidative stress, and the misfolding and aggregation of α-synuclein (α-syn) as key factors in disease initiation and progression. Many of these features of PD may be modeled in cells or animal models using the neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)). Reducing oxidative stress and nitric oxide synthase (NOS) activity has been shown to be protective in cell or animal models of MPP(+) toxicity. We have previously demonstrated that siRNA-mediated knockdown of α-syn lowers the activity of both dopamine transporter and NOS activity and protects dopaminergic neuron-like cells from MPP(+) toxicity. Here, we demonstrate that α-syn knockdown and modulators of oxidative stress/NOS activation protect cells from MPP(+)-induced toxicity via postmitochondrial mechanisms rather than by a rescue of the decrease in mitochondrial oxidative phosphorylation caused by MPP(+) exposure. We demonstrate that MPP(+) significantly decreases the synthesis of the antioxidant and obligate cofactor of NOS and TH tetrahydrobiopterin (BH4) through decreased cellular GTP/ATP levels. Furthermore, we demonstrate that RNAi knockdown of α-syn results in a nearly twofold increase in GTP cyclohydrolase I activity and a concomitant increase in basal BH4 levels. Together, these results demonstrate that both mitochondrial activity and α-syn play roles in modulating cellular BH4 levels.
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