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Title: | Synaptogyrin-3 Mediates Presynaptic Dysfunction Induced by Tau | Authors: | McInnes, Joseph Wierda, Keimpe Snellinx, An Bounti, Laura Wang, Yu-Chun STANCU, Ilie Cosmin Apostolo, Nuno Gevaert, Kris DEWACHTER, Ilse Spires-Jones, Tara L. De Strooper, Bart De Wit, Joris Zhou, Lujia Verstreken, Patrik |
Issue Date: | 2018 | Source: | NEURON, 97(4), p. 823-835 | Abstract: | 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. | Notes: | Verstreken, P (reprint author), VIB KU Leuven Ctr Brain & Dis Res, B-3000 Leuven, Belgium, patrik.verstreken@kuleuven.vib.be | Document URI: | http://hdl.handle.net/1942/26256 | ISSN: | 0896-6273 | e-ISSN: | 1097-4199 | DOI: | 10.1016/j.neuron.2018.01.022 | ISI #: | 000425713200011 | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2019 |
Appears in Collections: | Research publications |
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