Open AccessAcetaminophen Overdose as a Potential Risk Factor for Parkinson's Disease
Author(s) -
Bohler Sacha,
Liu Xiaosong,
Krauskopf Julian,
Caiment Florian,
Aubrecht Jiri,
Nicolaes Gerry A. F.,
Kleinjans Jos C. S.,
Briedé Jacco J.
Publication year - 2019
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.12663
Subject(s) - acetaminophen , pharmacology , substantia nigra , dopaminergic , parkinson's disease , amantadine , dopamine , chemistry , parkinsonism , modafinil , medicine , disease
Four complementary approaches were used to investigate acetaminophen overdose as a risk factor for Parkinson's disease ( PD ). Circulating microRNAs (mi RNA s) serum profiles from acetaminophen‐overdosed patients were compared with patients with terminal PD , revealing four shared mi RNA s. 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 Ch EMBL query identified proteins that are similarly targeted by DA and acetaminophen. Here, we highlight CYP 3A4, 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.