Adverse Outcome Pathway on Inhibition of the mitochondrial complex I of nigro-striatal neurons leading to parkinsonian motor deficits:
This AOP describes the linkage between inhibition of complex I (CI) of the mitochondrial respiratory chain and motor deficit as in parkinsonian disorders. Binding of an inhibitor to CI has been defined as the molecular initiating event (MIE) that triggers mitochondrial dysfunction, impaired proteost...
Gespeichert in:
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| Weitere Verfasser: | , , , , |
| Format: | Elektronisch E-Book |
| Sprache: | English |
| Veröffentlicht: |
Paris
OECD Publishing
2018
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| Schriftenreihe: | OECD Series on Adverse Outcome Pathways
no.7 |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Zusammenfassung: | This AOP describes the linkage between inhibition of complex I (CI) of the mitochondrial respiratory chain and motor deficit as in parkinsonian disorders. Binding of an inhibitor to CI has been defined as the molecular initiating event (MIE) that triggers mitochondrial dysfunction, impaired proteostasis, which then cause degeneration of dopaminergic (DA) neurons. Neuroinflammation is triggered early in the neurodegenerative process and exacerbates it significantly. These causatively linked cellular key events result in motor deficit symptoms, typical for parkinsonian disorders, including Parkinson's disease (PD), described as the Adverse Outcome (AO). The weight-of-evidence supporting the relationship between the described key events is based mainly on effects observed after an exposure to the chemicals rotenone and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This AOP could apply for chemicals having structural similarities to the stressors, chemicals binding to CI and supports the mechanistic biological plausibility in the process of evaluation and integration of the epidemiological studies into the risk assessment. |
| Beschreibung: | 1 Online-Ressource (184 p.) |
| DOI: | 10.1787/b46c3c00-en |
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| spelling | Bal-Price, Anna VerfasserIn aut Adverse Outcome Pathway on Inhibition of the mitochondrial complex I of nigro-striatal neurons leading to parkinsonian motor deficits Anna, Bal-Price ... [et al] Paris OECD Publishing 2018 1 Online-Ressource (184 p.) Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier OECD Series on Adverse Outcome Pathways no.7 This AOP describes the linkage between inhibition of complex I (CI) of the mitochondrial respiratory chain and motor deficit as in parkinsonian disorders. Binding of an inhibitor to CI has been defined as the molecular initiating event (MIE) that triggers mitochondrial dysfunction, impaired proteostasis, which then cause degeneration of dopaminergic (DA) neurons. Neuroinflammation is triggered early in the neurodegenerative process and exacerbates it significantly. These causatively linked cellular key events result in motor deficit symptoms, typical for parkinsonian disorders, including Parkinson's disease (PD), described as the Adverse Outcome (AO). The weight-of-evidence supporting the relationship between the described key events is based mainly on effects observed after an exposure to the chemicals rotenone and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This AOP could apply for chemicals having structural similarities to the stressors, chemicals binding to CI and supports the mechanistic biological plausibility in the process of evaluation and integration of the epidemiological studies into the risk assessment. Environment Social Issues/Migration/Health Leist, Marcel MitwirkendeR ctb Schildknecht, Stefan MitwirkendeR ctb Tschudi-Monnet, Florianne MitwirkendeR ctb Paini, Alicia MitwirkendeR ctb Terron, Andrea MitwirkendeR ctb FWS01 ZDB-13-SOC FWS_PDA_SOC https://doi.org/10.1787/b46c3c00-en Volltext |
| spellingShingle | Bal-Price, Anna Adverse Outcome Pathway on Inhibition of the mitochondrial complex I of nigro-striatal neurons leading to parkinsonian motor deficits Environment Social Issues/Migration/Health |
| title | Adverse Outcome Pathway on Inhibition of the mitochondrial complex I of nigro-striatal neurons leading to parkinsonian motor deficits |
| title_auth | Adverse Outcome Pathway on Inhibition of the mitochondrial complex I of nigro-striatal neurons leading to parkinsonian motor deficits |
| title_exact_search | Adverse Outcome Pathway on Inhibition of the mitochondrial complex I of nigro-striatal neurons leading to parkinsonian motor deficits |
| title_full | Adverse Outcome Pathway on Inhibition of the mitochondrial complex I of nigro-striatal neurons leading to parkinsonian motor deficits Anna, Bal-Price ... [et al] |
| title_fullStr | Adverse Outcome Pathway on Inhibition of the mitochondrial complex I of nigro-striatal neurons leading to parkinsonian motor deficits Anna, Bal-Price ... [et al] |
| title_full_unstemmed | Adverse Outcome Pathway on Inhibition of the mitochondrial complex I of nigro-striatal neurons leading to parkinsonian motor deficits Anna, Bal-Price ... [et al] |
| title_short | Adverse Outcome Pathway on Inhibition of the mitochondrial complex I of nigro-striatal neurons leading to parkinsonian motor deficits |
| title_sort | adverse outcome pathway on inhibition of the mitochondrial complex i of nigro striatal neurons leading to parkinsonian motor deficits |
| topic | Environment Social Issues/Migration/Health |
| topic_facet | Environment Social Issues/Migration/Health |
| url | https://doi.org/10.1787/b46c3c00-en |
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