Acetaminophen Overdose as a Potential Risk Factor for Parkinson's Disease
Four complementary approaches were used to investigate acetaminophen overdose as a risk factor for Parkinson's disease (PD). Circulating microRNAs (miRNAs) serum profiles from acetaminophen‐overdosed patients were compared with patients with terminal PD, revealing four shared miRNAs. Similariti...
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2019-11-01
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Online Access: | https://doi.org/10.1111/cts.12663 |
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doaj-c4299ed8807e4bb1b34aa2f0ebac37f42020-11-24T21:52:12ZengWileyClinical and Translational Science1752-80541752-80622019-11-0112660961610.1111/cts.12663Acetaminophen Overdose as a Potential Risk Factor for Parkinson's DiseaseSacha Bohler0Xiaosong Liu1Julian Krauskopf2Florian Caiment3Jiri Aubrecht4Gerry A. F. Nicolaes5Jos C. S. Kleinjans6Jacco J. Briedé7Department of Toxicogenomics Maastricht University Maastricht The NetherlandsDepartment of Biochemistry Maastricht University Maastricht The NetherlandsDepartment of Toxicogenomics Maastricht University Maastricht The NetherlandsDepartment of Toxicogenomics Maastricht University Maastricht The NetherlandsDrug & Safety R&D Pfizer Inc. Groton Connecticut USADepartment of Biochemistry Maastricht University Maastricht The NetherlandsDepartment of Toxicogenomics Maastricht University Maastricht The NetherlandsDepartment of Toxicogenomics Maastricht University Maastricht The NetherlandsFour complementary approaches were used to investigate acetaminophen overdose as a risk factor for Parkinson's disease (PD). Circulating microRNAs (miRNAs) serum profiles from acetaminophen‐overdosed patients were compared with patients with terminal PD, revealing four shared miRNAs. Similarities were found among molecular structures of dopamine (DA), acetaminophen, and two known PD inducers indicating affinity for dopaminergic transport. Potential interactions between acetaminophen and the human DA transporter were confirmed by molecular docking modeling and binding free energy calculations. Thus, it is plausible that acetaminophen is taken up by the dopaminergic transport system into the substantia nigra (SN). A ChEMBL query identified proteins that are similarly targeted by DA and acetaminophen. Here, we highlight CYP3A4, present in the SN, a predominant metabolizer of acetaminophen into its toxic metabolite N‐acetyl‐p‐benzoquinone imine and shown to be regulated in PD. Overall, based on our results, we hypothesize that overdosing of acetaminophen is a potential risk factor for parkinsonism.https://doi.org/10.1111/cts.12663 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sacha Bohler Xiaosong Liu Julian Krauskopf Florian Caiment Jiri Aubrecht Gerry A. F. Nicolaes Jos C. S. Kleinjans Jacco J. Briedé |
spellingShingle |
Sacha Bohler Xiaosong Liu Julian Krauskopf Florian Caiment Jiri Aubrecht Gerry A. F. Nicolaes Jos C. S. Kleinjans Jacco J. Briedé Acetaminophen Overdose as a Potential Risk Factor for Parkinson's Disease Clinical and Translational Science |
author_facet |
Sacha Bohler Xiaosong Liu Julian Krauskopf Florian Caiment Jiri Aubrecht Gerry A. F. Nicolaes Jos C. S. Kleinjans Jacco J. Briedé |
author_sort |
Sacha Bohler |
title |
Acetaminophen Overdose as a Potential Risk Factor for Parkinson's Disease |
title_short |
Acetaminophen Overdose as a Potential Risk Factor for Parkinson's Disease |
title_full |
Acetaminophen Overdose as a Potential Risk Factor for Parkinson's Disease |
title_fullStr |
Acetaminophen Overdose as a Potential Risk Factor for Parkinson's Disease |
title_full_unstemmed |
Acetaminophen Overdose as a Potential Risk Factor for Parkinson's Disease |
title_sort |
acetaminophen overdose as a potential risk factor for parkinson's disease |
publisher |
Wiley |
series |
Clinical and Translational Science |
issn |
1752-8054 1752-8062 |
publishDate |
2019-11-01 |
description |
Four complementary approaches were used to investigate acetaminophen overdose as a risk factor for Parkinson's disease (PD). Circulating microRNAs (miRNAs) serum profiles from acetaminophen‐overdosed patients were compared with patients with terminal PD, revealing four shared miRNAs. Similarities were found among molecular structures of dopamine (DA), acetaminophen, and two known PD inducers indicating affinity for dopaminergic transport. Potential interactions between acetaminophen and the human DA transporter were confirmed by molecular docking modeling and binding free energy calculations. Thus, it is plausible that acetaminophen is taken up by the dopaminergic transport system into the substantia nigra (SN). A ChEMBL query identified proteins that are similarly targeted by DA and acetaminophen. Here, we highlight CYP3A4, present in the SN, a predominant metabolizer of acetaminophen into its toxic metabolite N‐acetyl‐p‐benzoquinone imine and shown to be regulated in PD. Overall, based on our results, we hypothesize that overdosing of acetaminophen is a potential risk factor for parkinsonism. |
url |
https://doi.org/10.1111/cts.12663 |
work_keys_str_mv |
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