RT-DOb, a switch gene for the gene pair {Csf1r, Milr1}, can influence the onset of Alzheimer's disease by regulating communication between mast cell and microglia.

Nasibeh Khayer, Nasrin Motamed, Sayed-Amir Marashi, Fatemeh Goshadrou

PloS one 2023

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In biology, homeostasis is a central cellular phenomenon that plays a crucial role in survival. The central nervous system (CNS) is controlled by exquisitely sensitive homeostatic mechanisms when facing inflammatory or pathological insults. Mast cells and microglia play a crucial role in CNS homeostasis by eliminating damaged or unnecessary neurons and synapses. Therefore, decoding molecular circuits that regulate CNS homeostasis may lead to more effective therapeutic strategies that specifically target particular subsets for better therapy of Alzheimer's disease (AD). Based on a computational analysis of a microarray dataset related to AD, the H2-Ob gene was previously identified as a potential modulator of the homeostatic balance between mast cells and microglia. Specifically, it plays such a role in the presence of a three-way gene interaction in which the H2-Ob gene acts as a switch in the co-expression relationship of two genes, Csf1r and Milr1. Therefore, the importance of the H2-Ob gene as a potential therapeutic target for AD has led us to experimentally validate this relationship using the quantitative real-time PCR technique. In the experimental investigation, we confirmed that a change in the expression levels of the RT1-DOb gene (the rat ortholog of murine H2-Ob) can switch the co-expression relationship between Csf1r and Milr1. Furthermore, since the RT1-DOb gene is up-regulated in AD, the mentioned triplets might be related to triggering AD. Copyright: © 2023 Khayer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation

Nasibeh Khayer, Nasrin Motamed, Sayed-Amir Marashi, Fatemeh Goshadrou. RT-DOb, a switch gene for the gene pair {Csf1r, Milr1}, can influence the onset of Alzheimer's disease by regulating communication between mast cell and microglia. PloS one. 2023;18(7):e0288134