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http://hdl.handle.net/1942/26256
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DC Field | Value | Language |
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dc.contributor.author | McInnes, Joseph | - |
dc.contributor.author | Wierda, Keimpe | - |
dc.contributor.author | Snellinx, An | - |
dc.contributor.author | Bounti, Laura | - |
dc.contributor.author | Wang, Yu-Chun | - |
dc.contributor.author | STANCU, Ilie Cosmin | - |
dc.contributor.author | Apostolo, Nuno | - |
dc.contributor.author | Gevaert, Kris | - |
dc.contributor.author | DEWACHTER, Ilse | - |
dc.contributor.author | Spires-Jones, Tara L. | - |
dc.contributor.author | De Strooper, Bart | - |
dc.contributor.author | De Wit, Joris | - |
dc.contributor.author | Zhou, Lujia | - |
dc.contributor.author | Verstreken, Patrik | - |
dc.date.accessioned | 2018-06-29T10:13:02Z | - |
dc.date.available | 2018-06-29T10:13:02Z | - |
dc.date.issued | 2018 | - |
dc.identifier.citation | NEURON, 97(4), p. 823-835 | - |
dc.identifier.issn | 0896-6273 | - |
dc.identifier.uri | http://hdl.handle.net/1942/26256 | - |
dc.description.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. | - |
dc.description.sponsorship | We thank members of the Verstreken, De Wit, and De Strooper labs for advice. We thank J. Pauwels and F. Impens (VIB Proteomics Core) and K. Vennekens, K. Horre, K. Craessaerts, V. Hendrickx, and J. Verwaeren for assistance. We thank J.T. Littleton for Syngr knockout flies and antibodies. We gratefully acknowledge the patient donors and their families and thank the MRC Edinburgh Brain and Tissue bank. This work was supported by ERC CoG grants to P.V. and T.L.S.-J. (646671) and an ERC StG to J.D.W. (311083), the IWT, the Interuniversity Attraction Pole program by BELSPO (P7/16), a Methusalem grant of the Flemish government (METH/14/07), Opening the Future (LUF), the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO), Odysseus (FWO), IMI (IMPRIND), the UK Dementia Research Institute (Medical Research Council, Alzheimer's Society, and Alzheimer's Research UK), and VIB. P.V. and T.L.S.-J. are members of the FENS Kavli Network of Excellence. | - |
dc.language.iso | en | - |
dc.title | Synaptogyrin-3 Mediates Presynaptic Dysfunction Induced by Tau | - |
dc.type | Journal Contribution | - |
dc.identifier.epage | 835 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 823 | - |
dc.identifier.volume | 97 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | Verstreken, P (reprint author), VIB KU Leuven Ctr Brain & Dis Res, B-3000 Leuven, Belgium, patrik.verstreken@kuleuven.vib.be | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
dc.identifier.doi | 10.1016/j.neuron.2018.01.022 | - |
dc.identifier.isi | 000425713200011 | - |
item.fulltext | With Fulltext | - |
item.validation | ecoom 2019 | - |
item.accessRights | Restricted Access | - |
item.fullcitation | 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 (2018) Synaptogyrin-3 Mediates Presynaptic Dysfunction Induced by Tau. In: NEURON, 97(4), p. 823-835. | - |
item.contributor | McInnes, Joseph | - |
item.contributor | Wierda, Keimpe | - |
item.contributor | Snellinx, An | - |
item.contributor | Bounti, Laura | - |
item.contributor | Wang, Yu-Chun | - |
item.contributor | STANCU, Ilie Cosmin | - |
item.contributor | Apostolo, Nuno | - |
item.contributor | Gevaert, Kris | - |
item.contributor | DEWACHTER, Ilse | - |
item.contributor | Spires-Jones, Tara L. | - |
item.contributor | De Strooper, Bart | - |
item.contributor | De Wit, Joris | - |
item.contributor | Zhou, Lujia | - |
item.contributor | Verstreken, Patrik | - |
crisitem.journal.issn | 0896-6273 | - |
crisitem.journal.eissn | 1097-4199 | - |
Appears in Collections: | Research publications |
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1-s2.0-S0896627318300473-main.pdf Restricted Access | Published version | 4.29 MB | Adobe PDF | View/Open Request a copy |
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