Exploring a unique mutation in encephalopathies
Although rare, pediatric encephalopathies pose significant challenges due to the absence of well-established treatments. These disorders result from mutations in the most common brain subunit of a protein responsible for transmitting signals from the outside to the inside of a cell, Gαo. The large number of mutations involved limits the identification of universal therapeutic strategies and emphasizes the crucial need to understand each specific mutation in order to improve patient care.
A new variant with distinct mechanisms…
In their recent paper published in Cells, researchers from the laboratory of Prof. Vladimir Katanaev have investigated a unique mutation observed in two unrelated patients, that leads to seizures of different severity. Using a brain cell line, they uncovered distinct biochemical mechanisms of action and abnormal cellular localisation for this novel Gαo variant (as visible in the Figure below).
The normal protein is localized at the cell surface and in the Golgi compartment (in green, left picture), whereas the new variant loses its cell surface localisation (in green, right picture). © Adapted from Figure 7 in Larasati et al. 2023.
… but responsive to zinc
Building on their previous identification of zinc as a potential treatment avenue for certain pediatric encephalopathies, the research team explored the responsiveness of this new Gαo variant to zinc ions. Their in vitro experiments revealed a response to zinc, but with a different mechanism from previously tested variants. These findings set the stage for a more tailored and personalised approach to treatments, promising advances in the field of pediatric encephalopathy therapeutics.