@article{discovery10193867,
            year = {2024},
           month = {May},
          number = {6699},
          volume = {384},
            note = {This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.},
       publisher = {American Association for the Advancement of Science (AAAS)},
           title = {Pharmacological modulation of septins restores calcium homeostasis and is neuroprotective in models of Alzheimer's disease},
         journal = {Science},
            issn = {0036-8075},
        abstract = {Abnormal calcium signaling is a central pathological component of Alzheimer's disease (AD). Here, we describe the identification of a class of compounds called ReS19-T, which are able to restore calcium homeostasis in cell-based models of tau pathology. Aberrant tau accumulation leads to uncontrolled activation of store-operated calcium channels (SOCCs) by remodeling septin filaments at the cell cortex. Binding of ReS19-T to septins restores filament assembly in the disease state and restrains calcium entry through SOCCs. In amyloid-{\ensuremath{\beta}} and tau-driven mouse models of disease, ReS19-T agents restored synaptic plasticity, normalized brain network activity, and attenuated the development of both amyloid-{\ensuremath{\beta}} and tau pathology. Our findings identify the septin cytoskeleton as a potential therapeutic target for the development of disease-modifying AD treatments.},
          author = {Princen, Katrien and Van Dooren, Tom and van Gorsel, Marit and Louros, Nikolaos and Yang, Xiaojuan and Dumbacher, Michael and Bastiaens, Ilse and Coupet, Kristel and Dupont, Shana and Cuveliers, Eva and Lauwers, Annick and Laghmouchi, Mohamed and Vanwelden, Thomas and Carmans, Sofie and Van Damme, Nele and Duhamel, Hein and Vansteenkiste, Seppe and Prerad, Jovan and Pipeleers, Karolien and Rodiers, Olivier and De Ridder, Liese and Claes, Sofie and Busschots, Yoni and Pringels, Lentel and Verhelst, Vanessa and Debroux, Eveline and Brouwer, Marinka and Lievens, Sam and Tavernier, Jan and Farinelli, Melissa and Hughes-Asceri, Sandrine and Voets, Marieke and Winderickx, Joris and Wera, Stefaan and de Wit, Joris and Schymkowitz, Joost and Rousseau, Frederic and Zetterberg, Henrik and Cummings, Jeffrey L and Annaert, Wim and Cornelissen, Tom and De Winter, Hans and De Witte, Koen and Fivaz, Marc and Griffioen, Gerard},
             url = {https://doi.org/10.1126/science.add6260},
        keywords = {Animals, Humans, Mice, Alzheimer Disease, Amyloid beta-Peptides, Calcium, Calcium Channels, Calcium Signaling, Cytoskeleton, Disease Models, Animal, Homeostasis, Neuronal Plasticity, Neuroprotective Agents, Septins, tau Proteins}
}