Anna Scotto Rosato, Einar K Krogsaeter, Dawid Jaślan, Carla Abrahamian, Sandro Montefusco, Chiara Soldati, Barbara Spix, Maria Teresa Pizzo, Giuseppina Grieco, Julia Böck, Amanda Wyatt, Daniela Wünkhaus, Marcel Passon, Marc Stieglitz, Marco Keller, Guido Hermey, Sandra Markmann, Doris Gruber-Schoffnegger, Susan Cotman, Ludger Johannes, Dennis Crusius, Ulrich Boehm, Christian Wahl-Schott, Martin Biel, Franz Bracher, Elvira De Leonibus, Elena Polishchuk, Diego L Medina, Dominik Paquet, Christian Grimm
Lysosomes are cell organelles that degrade macromolecules to recycle their components. If lysosomal degradative function is impaired, e.g., due to mutations in lysosomal enzymes or membrane proteins, lysosomal storage diseases (LSDs) can develop. LSDs manifest often with neurodegenerative symptoms, typically starting in early childhood, and going along with a strongly reduced life expectancy and quality of life. We show here that small molecule activation of the Ca2+ -permeable endolysosomal two-pore channel 2 (TPC2) results in an amelioration of cellular phenotypes associated with LSDs such as cholesterol or lipofuscin accumulation, or the formation of abnormal vacuoles seen by electron microscopy...
September 7, 2022: EMBO Molecular Medicine