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Papers of the Week

Papers: 14 Mar 2020 - 20 Mar 2020

Animal Studies, Pharmacology/Drug Development

2020 Mar 17

Cell Rep



Morphine and Naloxone Facilitate Neural Stem Cells Proliferation via a TET1-Dependent and Receptor-Independent Pathway.


Liang L, Chen J, Li Y, Lai X, Sun H, Li C, Zhang M, Yang T, Meng F, Law P-Y, Loh HH, Zheng H
Cell Rep. 2020 Mar 17; 30(11):3625-3631.e6.
PMID: 32187535.


Normally, opioids function in a receptor-dependent manner. They bind to opioid receptors, activate or inhibit receptor activation, and subsequently modulate downstream signal transduction. However, the complex functions of opioids and the low expression of opioid receptors and their endogenous peptide agonists in neural stem cells (NSCs) suggest that some opioids may also modulate NSCs via a receptor-independent pathway. In the current study, two opioids, morphine and naloxone, are demonstrated to facilitate NSC proliferation via a receptor-independent and ten-eleven translocation methylcytosine dioxygenase 1 (TET1)-dependent pathway. Morphine and naloxone penetrate cell membrane, bind to TET1 protein via three key residues (1,880-1,882), and subsequently result in facilitated proliferation of NSCs. In addition, the two opioids also inhibit the DNA demethylation ability of TET1. In summary, the current results connect opioids and DNA demethylation directly at least in NSCs and extend our understanding on both opioids and NSCs.