Discovery could lead to new therapeutic targets for neurodegenerative diseases

Research led by Drs. Miguel Burguillos (University of Seville, Spain) and Miguel Branco (Queen Mary University of London, UK), has revealed new findings about mechanisms regulating brain inflammation which open a new pathway in the field of neuroinflammation.

This is important because in neurodegenerative diseases such as Parkinson´s and Alzheimer´s diseases, where there is no effective treatment yet, it is considered that microglia play a key role in their pathology and progression. Therefore, discovery of new mechanisms regulating microglial function could become new therapeutic targets to use in clinic. The findings are now published in the scientific journal Cell Reports.

The authors found that a protein called TET2 is responsible for modulating the immune response generated in the immune cells (named microglia) in the brain, under inflammatory conditions. The authors observe that in transgenic mice lacking TET2 specifically in microglia cells, the neuroinflammatory response is hampered in an neuroinflammatory model. Normally TET2, together with other proteins, regulates the activity of genes by removing certain chemical marks from DNA, but the authors found that this mechanism was not behind the role of TET2 in microglia.

TET2 appears to act in microglia by a different mechanism to that seen in other cells that mediate inflammation outside of the brain.
Miguel Branco, a Senior Lecturer at Queen Mary University of London

We observe that microglia cells in a proinflammatory environment increase the expression of TET2, and this protein becomes a key regulator for many of the changes that leads to the full activation of these cells.
Miguel Burguillos, a Ramón y Cajal Fellow at University of Seville

Although this is an exploratory study, the new mechanism described in this paper opens a new route in the research of mechanisms governing microglia under disease conditions. Thus, TET2 could become a significant component for different neurodegenerative disease such as Parkinson´s disease and Alzheimer´s disease where neuroinflammation driven by microglia contributes to their pathology.

University of Seville

Journal reference:

Carrillo-Jimenez, A. et al. (2019) TET2 Regulates the Neuroinflammatory Response in Microglia. Cell Reports. doi.org/10.1016/j.celrep.2019.09.013