ArticleScience (New York, N.Y.)2024
Pharmacological modulation of septins restores calcium homeostasis and is neuroprotective in models of Alzheimer's disease.
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Article in Science (New York, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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35citing papers in PubMed, 1 pooled it
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Unraveling the Controversy: The Causal Link Between Osteoarthritis and Alzheimer's Disease.Brain and behavior · 2025Pooled it
- Randomized phase 2a trial assessing a novel septin molecular glue in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Trial
- Design, synthesis and biological evaluation of donepezil-safinamide hybrids as dual AChE and MAO-B inhibitor for Alzheimer's disease treatment.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Calcium Overloading-Induced UBE2O Upregulation Alleviates Neuronal Apoptosis.Molecular neurobiology · 2026Article
- PIGBOS-CLCC1 interaction shapes cellular calcium dynamics and energy metabolism.Cell communication and signaling : CCS · 2026Article
- Oxiracetam Improves Cognitive Disorder in AD by Modulating AMPAR Subunits GluA1/GluA2 Kinetics.Cell biochemistry and biophysics · 2026Article
- Calbindin-D28k deficiency mediates tau-driven hippocampal hyperexcitement and cognitive impairment.Translational neurodegeneration · 2026Article
- Three-dimensional interactive network: Mitochondrial-metabolic-calcium homeostasis driving Alzheimer's disease.Genes & diseases · 2026Review
- Dynamic-Structure Redesign of Calmodulin Reveals Mechanistic Constraints on Ryr2 Regulation.bioRxiv : the preprint server for biology · 2026Article
- Comparative Analysis of Septin Modifiers, Forchlorfenuron and UR214-9, on Mitochondrial Fragmentation and Lytic Cell Death.Cytoskeleton (Hoboken, N.J.) · 2026Article
- Kinesin-1 is highly flexible and adopts an open conformation in the absence of cargo.iScience · 2026Article
- Surrogates of glymphatic metrics decline and coupled sleep rhythms disruption in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Oral Exposure to Food-Grade Nanoparticles Poses a Risk of Alzheimer's Disease-Like Symptoms by Triggering Autophagy Defects in Neurons.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The role of apolipoprotein E4 on calcium homeostasis in primary hippocampal neurons: anFrontiers in neuroscience · 2026Article
- Pretangle tau pathology accrual in the default mode network during the progression of Alzheimer's disease.Molecular neurodegeneration advances · 2026Article
- Calcium signaling hypothesis: A non-negligible pathogenesis in Alzheimer's disease.Journal of advanced research · 2025Review
- Sex-specific associations of gene expression with Alzheimer's disease neuropathology and ante-mortem cognitive performance.Nature communications · 2025Article
- Septins in the nervous system: from cytoskeletal dynamics to neurological disorders.Cell communication and signaling : CCS · 2025Review
- Septin organization is regulated by the Gpa1 ubiquitination domain and endocytic machinery during the yeast pheromone response.Molecular biology of the cell · 2025Article
- Tau-Targeted Therapeutic Strategies: Mechanistic Targets, Clinical Pipelines, and Analysis of Failures.Cells · 2025Review
Corrections and comments
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Authors and funding
45 authors.
Katrien Princen *reMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.ORCID 0000-0002-7209-6422
Tom Van Dooren *reMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.ORCID 0009-0003-1054-0297
Marit van GorselreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.ORCID 0009-0000-6889-0693
Nikolaos LourosSwitch Laboratory, VIB Center for Brain and Disease Research, 3000 Leuven, Belgium.ORCID 0000-0002-4030-1022
Xiaojuan YangLaboratory for Membrane Trafficking, VIB-Center for Brain and Disease Research and Department of Neurosciences, Leuven Brain Institute, 3000 Leuven, Belgium.ORCID 0000-0002-7534-011X
Michael DumbacherreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.
Ilse BastiaensreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.
Kristel CoupetreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.
Shana DupontreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.
Eva CuveliersreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.ORCID 0009-0004-7619-0901
Annick LauwersreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.ORCID 0009-0002-6172-737X
Mohamed LaghmouchireMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.
Thomas VanweldenreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.
Sofie CarmansreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.
Nele Van DammereMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.ORCID 0000-0003-3882-6222
Hein DuhamelreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.ORCID 0009-0008-6921-7220
Seppe VansteenkistereMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.
Jovan PreradreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.
Karolien PipeleersreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.
Olivier RodiersreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.
Liese De RidderreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.
Sofie ClaesreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.
Yoni BusschotsreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.
Lentel PringelsreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.
Vanessa VerhelstreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.ORCID 0009-0000-7202-1423
Eveline DebrouxreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.ORCID 0009-0005-2718-5580
Marinka BrouwerLaboratory of Synapse Biology, VIB Center for Brain & Disease Research and KU Leuven Department of Neurosciences, Leuven Brain Institute, 3000 Leuven, Belgium.
Sam LievensCytokine Receptor Lab, VIB Center for Medical Biotechnology, 9052 Ghent, Belgium.
Jan TavernierCytokine Receptor Lab, VIB Center for Medical Biotechnology, 9052 Ghent, Belgium.
Melissa FarinelliE-PHY-SCIENCE, Bioparc Sophia-Antipolis, 06410 Biot, France.ORCID 0000-0003-1204-1435
Sandrine Hughes-AsceriE-PHY-SCIENCE, Bioparc Sophia-Antipolis, 06410 Biot, France.ORCID 0009-0008-8724-0686
Marieke VoetsreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.ORCID 0000-0003-1329-3407
Joris WinderickxreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.ORCID 0000-0003-3133-7733
Stefaan WerareMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.
Joris de WitLaboratory of Synapse Biology, VIB Center for Brain & Disease Research and KU Leuven Department of Neurosciences, Leuven Brain Institute, 3000 Leuven, Belgium.ORCID 0000-0003-1120-1089
Joost SchymkowitzSwitch Laboratory, VIB Center for Brain and Disease Research, 3000 Leuven, Belgium.ORCID 0000-0003-2020-0168
Frederic RousseauSwitch Laboratory, VIB Center for Brain and Disease Research, 3000 Leuven, Belgium.ORCID 0000-0002-9189-7399
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, S-431 80 Mölndal, Sweden.ORCID 0000-0003-3930-4354
Jeffrey L CummingsChambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas, NV 89154, USA.ORCID 0000-0001-8944-4158
Wim AnnaertLaboratory for Membrane Trafficking, VIB-Center for Brain and Disease Research and Department of Neurosciences, Leuven Brain Institute, 3000 Leuven, Belgium.ORCID 0000-0003-0150-9661
Tom CornelissenreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.ORCID 0000-0003-0738-5452
Hans De WinterLaboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, 2610 Wilrijk, Belgium.ORCID 0000-0002-4450-7677
Koen De WittereMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.
Marc FivazreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.ORCID 0000-0003-1003-7934
Gerard GriffioenreMYND NV, Bio-Incubator, 3001 Leuven-Heverlee, Belgium.ORCID 0000-0003-2492-6046
Funding
Trial-Ready Cohort for Preclinical/Prodromal Alzheimer's DiseaseR01AG053798 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI AISEN, PAUL S., CUMMINGS, JEFFREY L. · 2017 to 2022
$39.4MTranslational and Therapeutics CoreP30AG072959 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI JAGAN AYYAPPAN PILLAI · 2021 to 2026
$23.9MRenewal of Centers of Biomedical Research Excellence (COBRE) (Phase 2) CNTN - ResubmissionP20GM109025 · NIGMS · CLEVELAND CLINIC FOUNDATION · PI JESSICA KIRKLAND CALDWELL · 2015 to 2026
$22.8MChronic Traumatic Encephalopathy: Detection, Diagnosis, Course, and Risk FactorsU01NS093334 · NINDS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI CUMMINGS, JEFFREY L., REIMAN, ERIC MICHAEL · 2016 to 2022
$17.0MAlzheimer's Clinical Trial InnOvatioN (ACTION) InitiativeR35AG071476 · NIA · UNIVERSITY OF NEVADA LAS VEGAS · PI CUMMINGS, JEFFREY L. · 2021 to 2025
$2.9MAlzheimer's Disease and Related Dementias Innovation Incubator (InnovaTor)R25AG083721 · NIA · UNIVERSITY OF NEVADA LAS VEGAS · PI JEFFREY L. CUMMINGS, Xue K Zhong · 2023 to 2026
$1.0MNIA NIH HHS P30 AG072959NIA NIH HHS R01 AG053798NIA NIH HHS R25 AG083721NIA NIH HHS R35 AG071476NIGMS NIH HHS P20 GM109025NINDS NIH HHS U01 NS093334
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.
Indexed as
Alzheimer DiseaseAmyloid beta-PeptidesCalciumHomeostasisNeuroprotective AgentsSeptinstau ProteinsAnimalsCalcium ChannelsCalcium SignalingCytoskeletonDisease Models, AnimalHumansMiceNeuronal PlasticityAmyloid beta-PeptidesCalciumCalcium ChannelsNeuroprotective AgentsSeptinstau Proteins
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.