Gancyclovir

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Gancyclovir (brand name Cytovene) is an antiviral drug with activity against cytomegalovirus.[citation needed]

A 2014 study in mice suggested gancyclovir reduced microglial activation;[1] however follow-up mice studies and in vitro research found it did not have this effect.[2]

The authors of the 2014 paper later published a follow-up paper (2017) based on in vitro and in vivo experiments using ganciclovir. This time they found a potentially pro-inflammatory response, specifically that ganciclovir, in sufficient doses, might stimulate a type-I interferon response in microglia. The authors attributed this response to a DNA-sensing protein called STING. While this result might appear to contradict their earlier anti-neuroinflammatory finding, they suggest it could indicate ganciclovir (GCV) "can exhibit dual function in microglia [...]: in naïve state, GCV induces microglia to be 'primed'; on the other hand, GCV reduces inflammation in active microglia."[3]

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References[edit | edit source]

  1. ↑ Ding, Zhaoqing; Mathur, Vidhu; Ho, Peggy P.; James, Michelle L.; Lucin, Kurt M.; Hoehne, Aileen; Alabsi, Haitham; Gambhir, Sanjiv S.; Steinman, Lawrence (February 10, 2014). "Antiviral drug ganciclovir is a potent inhibitor of microglial proliferation and neuroinflammation". The Journal of Experimental Medicine. 211 (2): 189–198. doi:10.1084/jem.20120696. ISSN 1540-9538. PMC 3920559. PMID 24493798.
  2. ↑ Skripuletz, Thomas; Salinas Tejedor, Laura; Prajeeth, Chittappen K.; Hansmann, Florian; Chhatbar, Chintan; Kucman, Valeria; Zhang, Ning; Raddatz, Barbara B.; Detje, Claudia N. (October 8, 2015). "The antiviral drug ganciclovir does not inhibit microglial proliferation and activation". Scientific Reports. 5. doi:10.1038/srep14935. ISSN 2045-2322. PMC 4597339. PMID 26447351.
  3. ↑ Mathur, Vidhu; Burai, Ritwik; Vest, Ryan T.; Bonanno, Liana N.; Lehallier, Benoit; Zardeneta, Macy; Mistry, Karishma N.; Do, Danny; Marsh, Samuel E. (December 20, 2017). "Activation of the STING-dependent type I interferon response reduces microglial reactivity and neuroinflammation". Neuron. 96 (6): 1290–1302.e6. doi:10.1016/j.neuron.2017.11.032. ISSN 0896-6273. PMC 5806703. PMID 29268096.

microglia A type of immune cell, called a macrophage, that lives in the brain. For historical reasons, macrophages have different names based on the part of the body that they normally live in. Macrophages that normally live in the blood are called monocytes. Macrophages that normally live in the skin are called Langerhans cells. Macrophages that normally live in the liver are called Kupffer cells. And macrophages that normally live in the central nervous system are called microglia. Microglia were originally classified as glial cells, under the assumption that the cells had a merely structural function, before it was realized that the cells were in fact immune cells. As the "sentinel cells" of the central nervous system, microglia survey their environment for abnormalities such as infection or tissue damage, and then initiate an immune response to fight the infection or repair the tissue damage.

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