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Synaptogyrin-3 Mediates Presynaptic Dysfunction Induced by Tau
Open accessAbstract
Synaptic dysfunction is an early pathological feature of neurodegenerative diseases associated with Tau, including Alzheimer's disease. Interfering with early synaptic dysfunction may be therapeutically beneficial to prevent cognitive decline and disease progression, but the mechanisms underlying synaptic defects associated with Tau are unclear. In disease conditions, Tau mislocalizes into pre- and postsynaptic compartments; here we show that, under pathological conditions, Tau binds to presynaptic vesicles in Alzheimer's disease patient brain. We define that the binding of Tau to synaptic vesicles is mediated by the transmembrane vesicle protein Synaptogyrin-3. In fly and mouse models of Tauopathy, reduction of Synaptogyrin-3 prevents the association of presynaptic Tau with vesicles, alleviates Tau-induced defects in vesicle mobility, and restores neurotransmitter release. This work therefore identifies Synaptogyrin-3 as the binding partner of Tau on synaptic vesicles, revealing a new presynapse-specific Tau interactor, which may contribute to early synaptic dysfunction in neurodegenerative diseases associated with Tau.
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“Tau, including phosphorylated tau, is present in presynaptic and postsynaptic compartments in the PS19 mouse model (Yoshiyama et al., 2007, Dejanovic et al., 2018, McInnes et al., 2018).”
From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as McInnes et al., 2018
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“Meanwhile, the extracellular tau can be taken up by neighboring cells, both neurons and glial cells, through various pathways, including phagocytosis [68], macropinocytosis [69], receptor-mediated uptake [67, 70], endocytosis [71], and/or membrane fusion of exosomes [72, 73].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [68]
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Metadata
- Authors
- McInnes, J., Wierda, K., Snellinx, A., Bounti, L., Wang, Y.-C., Stancu, I.-C., Apóstolo, N., Gevaert, K., Dewachter, I., Spires-Jones, T. L., De Strooper, B., De Wit, J., Zhou, L., & Verstreken, P.
- Affiliations
- VIB-KU Leuven Center for Brain & Disease Research (BE)
- Hasselt University (BE)
- Ghent University (BE)
- Corresponding author
- Verstreken, Patrik
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 97
- Issue
- 4
- Pages
- 823-835.e8
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2785931320
- Cited by
- 242
- References
- 55
- Citations by year
- 2026: 17 · 2025: 28 · 2024: 42 · 2023: 31 · 2022: 26 · 2021: 33 · 2020: 27 · 2019: 25 · 2018: 12
- FWCI
- 16.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion, other-oa)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Digital Access to Libraries (submittedVersion, other-oa)
- Document Server@UHasselt (UHasselt) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc-nd)
- Funders
- ERC CoG (646671)
- ERC StG (311083)
- IWT
- Interuniversity Attraction Pole program by BELSPO (P7/16)
- Methusalem grant of the Flemish government (METH/14/07)
- Opening the Future
- Fonds voor Wetenschappelijk Onderzoek Vlaanderen
- Odysseus
- IMI
- UK Dementia Research Institute
- VIB
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- tau protein, presynaptic dysfunction, synaptic vesicles, Alzheimer's disease, tauopathy, neurotransmitter release, vesicle mobility, synaptic dysfunction, neurodegenerative diseases, protein-protein interaction
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Drosophila melanogaster, Female, Hippocampus, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Synaptic Vesicles, tau Proteins, Presynaptic Terminals, Tauopathies, Drosophila Proteins, Primary Cell Culture, Synaptogyrins
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