ArticleThe Journal of biological chemistry2013
Metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by mitochondrion-targeted cytochrome P450 2D6: implications in Parkinson disease.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 75 citations in OpenAlex.
- Beyond the Brain: Exploring the multi-organ axes in Parkinson's disease pathogenesis.Journal of advanced research · 2026Review
- Developmental exposure of zebrafish to 1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) elicits MPTP-like neurotoxicity.Neurotoxicology · 2025Article
- m5C-modified circRREB1 promotes lung cancer progression by inducing mitophagy.Journal of experimental & clinical cancer research : CR · 2025Article
- Reduced levels of nitrated α-synuclein in the protective effect of harpagoside on rotenone-induced cellular models of Parkinson's disease.Frontiers in cell and developmental biology · 2025Article
- Methodological Approaches to Experimental Evaluation of Neuroprotective Action of Potential Drugs.International journal of molecular sciences · 2024Review
- Exploring the Regulation of Cytochrome P450 in SH-SY5Y Cells: Implications for the Onset of Neurodegenerative Diseases.International journal of molecular sciences · 2024Article
- Positive Tetrahydrocurcumin-Associated Brain-Related Metabolomic Implications.Molecules (Basel, Switzerland) · 2023Review
- Quantitative and causal analysis for inflammatory genes and the risk of Parkinson's disease.Frontiers in immunology · 2023Article
- Roles of selected non-P450 human oxidoreductase enzymes in protective and toxic effects of chemicals: review and compilation of reactions.Archives of toxicology · 2022Review
- Mechanistic Insights Expatiating the Redox-Active-Metal-Mediated Neuronal Degeneration in Parkinson's Disease.International journal of molecular sciences · 2022Review
- Elucidating the Neuroprotective Role of PPARs in Parkinson's Disease: A Neoteric and Prospective Target.International journal of molecular sciences · 2021Review
- The Promise of the Zebrafish Model for Parkinson's Disease: Today's Science and Tomorrow's Treatment.Frontiers in genetics · 2021Review
- β-Naphthoflavone and Ethanol Reverse Mitochondrial Dysfunction in A Parkinsonian Model of Neurodegeneration.International journal of molecular sciences · 2020Article
- Measurement of baseline locomotion and other behavioral traits in a common marmoset model of Parkinson's disease established by a single administration regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: providing reference data for efficacious preclinical evaluations.Behavioural pharmacology · 2020Article
- Curcumin-Activated Mesenchymal Stem Cells Derived from Human Umbilical Cord and Their Effects on MPTP-Mouse Model of Parkinson's Disease: A New Biological Therapy for Parkinson's Disease.Stem cells international · 2020Article
- Mitochondrially targeted cytochrome P450 2D6 is involved in monomethylamine-induced neuronal damage in mouse models.The Journal of biological chemistry · 2019Article
- δ-Opioid Receptor Activation Attenuates the Oligomer Formation Induced by Hypoxia and/or α-Synuclein Overexpression/Mutation Through Dual Signaling Pathways.Molecular neurobiology · 2019Article
- The regulation of drug-metabolizing enzymes and membrane transporters by inflammation: Evidences in inflammatory diseases and age-related disorders.Journal of food and drug analysis · 2019Review
- No Country for Old Worms: A Systematic Review of the Application ofMetabolites · 2018Review
- β-Naphtoflavone and Ethanol Induce Cytochrome P450 and Protect towards MPP⁺ Toxicity in Human Neuroblastoma SH-SY5Y Cells.International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxic side product formed in the chemical synthesis of desmethylprodine opioid analgesic, which induces Parkinson disease. Monoamine oxidase B, present in the mitochondrial outer membrane of glial cells, catalyzes the oxidation of MPTP to the toxic 1-methyl-4-phenylpyridinium ion (MPP(+)), which then targets the dopaminergic neurons causing neuronal death. Here, we demonstrate that mitochondrion-targeted human cytochrome P450 2D6 (CYP2D6), supported by mitochondrial adrenodoxin and adrenodoxin reductase, can efficiently catalyze the metabolism of MPTP to MPP(+), as shown with purified enzymes and also in cells expressing mitochondrial CYP2D6. Neuro-2A cells stably expressing predominantly mitochondrion-targeted CYP2D6 were more sensitive to MPTP-mediated mitochondrial respiratory dysfunction and complex I inhibition than cells expressing predominantly endoplasmic reticulum-targeted CYP2D6. Mitochondrial CYP2D6 expressing Neuro-2A cells produced higher levels of reactive oxygen species and showed abnormal mitochondrial structures. MPTP treatment also induced mitochondrial translocation of an autophagic marker, Parkin, and a mitochondrial fission marker, Drp1, in differentiated neurons expressing mitochondrial CYP2D6. MPTP-mediated toxicity in primary dopaminergic neurons was attenuated by CYP2D6 inhibitor, quinidine, and also partly by monoamine oxidase B inhibitors deprenyl and pargyline. These studies show for the first time that dopaminergic neurons expressing mitochondrial CYP2D6 are fully capable of activating the pro-neurotoxin MPTP and inducing neuronal damage, which is effectively prevented by the CYP2D6 inhibitor quinidine.
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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.