2 April, 2022

Transmembrane Glycoprotein Alteration (Basic Research)

ALTERATION OF THE CD200-CD200R1 IN HUNTINGTON’S DISEASE IS DESCRIBED FOR THE FIRST TIME

Creatio’s scientists describe, for the first time, dysregulation in the off-signaling between neurons and microglia in Huntington’s disease (HD).

In the paper recently published by Comella et al., we describe alterations in the temporal expression pattern of CD200-CD200R1 in both the CNS and blood in a transgenic mouse model of HD, the R6/1. In a healthy brain, neuro-microglia crosstalk is maintained through different signaling pathways, notably through the interaction between the transmembrane glycoprotein ligand CD200 and its receptor CD200R1. The CD200-CD200R1 system is often altered in animal models of physiological aging or neurological disorders (such as multiple sclerosis, Parkinson’s disease, depression, stress, and CNS infections) and in neurological symptoms of peripheral immune system activation. Hence, due to the lack of knowledge about neuronal-microglial communication in HD, and specifically about the CD200-CD200R1 system, Creatio prompted to investigate the expression of both the ligand and the receptor in HD mouse models to provide further insight into the function of the neuroimmune system in HD.

Comella and coworkers demonstrated an increase in CD200 gene expression and protein levels in the brain parenchyma along with HD pathogenesis progression in R6/1 mice. Interestingly, the expression of CD200 mRNA was also up-regulated in peripheral blood following a similar temporal pattern than the CD200 levels observed in the CNS. No alterations of CD200R1 expression were detected, suggesting that canonical neuro-microglial communication through CD200-CD200R1 interaction is not compromised, and that CD200 up-regulation in R6/1 brain parenchyma could represent a neurotrophic signal to sustain or extend neuronal function in the latest stages of HD as a pro-survival mechanism.

Creatio is confident in continuing this research line regarding the study of neuro-microglia interactions, particularly the CD200 as a possible pro-survival mechanism in HD pathogenesis. Elucidating the mechanisms of the interactions between neurons and microglia will provide novel therapeutic strategies to treat HD, a neurodegenerative condition with no effective, available therapy at the moment.