eprintid: 10193867 rev_number: 9 eprint_status: archive userid: 699 dir: disk0/10/19/38/67 datestamp: 2024-06-28 09:34:35 lastmod: 2024-06-28 09:34:35 status_changed: 2024-06-28 09:34:35 type: article metadata_visibility: show sword_depositor: 699 creators_name: Princen, Katrien creators_name: Van Dooren, Tom creators_name: van Gorsel, Marit creators_name: Louros, Nikolaos creators_name: Yang, Xiaojuan creators_name: Dumbacher, Michael creators_name: Bastiaens, Ilse creators_name: Coupet, Kristel creators_name: Dupont, Shana creators_name: Cuveliers, Eva creators_name: Lauwers, Annick creators_name: Laghmouchi, Mohamed creators_name: Vanwelden, Thomas creators_name: Carmans, Sofie creators_name: Van Damme, Nele creators_name: Duhamel, Hein creators_name: Vansteenkiste, Seppe creators_name: Prerad, Jovan creators_name: Pipeleers, Karolien creators_name: Rodiers, Olivier creators_name: De Ridder, Liese creators_name: Claes, Sofie creators_name: Busschots, Yoni creators_name: Pringels, Lentel creators_name: Verhelst, Vanessa creators_name: Debroux, Eveline creators_name: Brouwer, Marinka creators_name: Lievens, Sam creators_name: Tavernier, Jan creators_name: Farinelli, Melissa creators_name: Hughes-Asceri, Sandrine creators_name: Voets, Marieke creators_name: Winderickx, Joris creators_name: Wera, Stefaan creators_name: de Wit, Joris creators_name: Schymkowitz, Joost creators_name: Rousseau, Frederic creators_name: Zetterberg, Henrik creators_name: Cummings, Jeffrey L creators_name: Annaert, Wim creators_name: Cornelissen, Tom creators_name: De Winter, Hans creators_name: De Witte, Koen creators_name: Fivaz, Marc creators_name: Griffioen, Gerard title: Pharmacological modulation of septins restores calcium homeostasis and is neuroprotective in models of Alzheimer's disease ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F86 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 note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. 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-β and tau-driven mouse models of disease, ReS19-T agents restored synaptic plasticity, normalized brain network activity, and attenuated the development of both amyloid-β and tau pathology. Our findings identify the septin cytoskeleton as a potential therapeutic target for the development of disease-modifying AD treatments. date: 2024-05-31 date_type: published publisher: American Association for the Advancement of Science (AAAS) official_url: https://doi.org/10.1126/science.add6260 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2284840 doi: 10.1126/science.add6260 medium: Print-Electronic lyricists_name: Zetterberg, Henrik lyricists_id: HZETT94 actors_name: Zetterberg, Henrik actors_name: Harriot, Anne-Marie actors_id: HZETT94 actors_id: AHARA72 actors_role: owner actors_role: impersonator full_text_status: public publication: Science volume: 384 number: 6699 article_number: eadd6260 event_location: United States issn: 0036-8075 citation: Princen, Katrien; Van Dooren, Tom; van Gorsel, Marit; Louros, Nikolaos; Yang, Xiaojuan; Dumbacher, Michael; Bastiaens, Ilse; ... Griffioen, Gerard; + view all <#> Princen, Katrien; Van Dooren, Tom; van Gorsel, Marit; Louros, Nikolaos; Yang, Xiaojuan; Dumbacher, Michael; Bastiaens, Ilse; Coupet, Kristel; Dupont, Shana; Cuveliers, Eva; Lauwers, Annick; Laghmouchi, Mohamed; Vanwelden, Thomas; Carmans, Sofie; Van Damme, Nele; Duhamel, Hein; Vansteenkiste, Seppe; Prerad, Jovan; Pipeleers, Karolien; Rodiers, Olivier; De Ridder, Liese; Claes, Sofie; Busschots, Yoni; Pringels, Lentel; Verhelst, Vanessa; Debroux, Eveline; Brouwer, Marinka; Lievens, Sam; Tavernier, Jan; Farinelli, Melissa; Hughes-Asceri, Sandrine; Voets, Marieke; Winderickx, Joris; Wera, Stefaan; de Wit, Joris; Schymkowitz, Joost; Rousseau, Frederic; Zetterberg, Henrik; Cummings, Jeffrey L; Annaert, Wim; Cornelissen, Tom; De Winter, Hans; De Witte, Koen; Fivaz, Marc; Griffioen, Gerard; - view fewer <#> (2024) Pharmacological modulation of septins restores calcium homeostasis and is neuroprotective in models of Alzheimer's disease. Science , 384 (6699) , Article eadd6260. 10.1126/science.add6260 <https://doi.org/10.1126/science.add6260>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10193867/2/Zetterberg_Princen.pdf