This paper, published in the journal Human Molecular Genetics, addresses the pathophysiology of megalencephalic leukoencephalopathy (MLC) in astrocytes. Its main authors are Sonia Sirisi, Xabier Elorza–Vidal and Tanit Arnedo – affiliated to UB–IDIBELL and CIBERER. The work was co–directed by Xavier Gasull (Institute of Neurosciences–UB and IDIBAPS) and Raúl Estévez (Institute of Neurosciences–UB, IDIBELL and CIBERER), in collaboration with Virginia Nunes (UB, IDIBELL and CIBERER).

The study concluded that ClC–2 (chloride channel), GlialCAM and MLC1 proteins (the latter two are altered in MLC) associate to form a ternary complex when astrocytes are depolarized, such as in situations of high neuronal activity. This association changes the voltage activation of the ClC–2 channel, which leads it to be open to positive potentials, allowing it to participate in the compensation of positive charges in the glial cells introducing chloride.

Thus this work assigns a physiological function to the ClC–2 channel and allows to describe an altered pathophysiological process in MLC, which is necessary to design future therapeutic interventions. This work also hypothesizes what the biochemical function of GlialCAM/MLC1 proteins might be.