Please use this identifier to cite or link to this item:
|Title:||Tau association with synaptic vesicles causes presynaptic dysfunction||Authors:||Zhou, Lujia
Herrmann, Abigail G.
Jackson, Rosemary J.
De Strooper, Bart
Spires-Jones, Tara L.
De Wit, Joris
|Issue Date:||2017||Source:||Nature Communications, 11(8), p. 1-13 (Art N° 15295)||Abstract:||Tau is implicated in more than 20 neurodegenerative diseases, including Alzheimer’s disease. Under pathological conditions, Tau dissociates from axonal microtubules and missorts to pre- and postsynaptic terminals. Patients suffer from early synaptic dysfunction prior to Tau aggregate formation, but the underlying mechanism is unclear. Here we show that pathogenic Tau binds to synaptic vesicles via its N-terminal domain and interferes with presynaptic functions, including synaptic vesicle mobility and release rate, lowering neurotransmission in fly and rat neurons. Pathological Tau mutants lacking the vesicle binding domain still localize to the presynaptic compartment but do not impair synaptic function in fly neurons. Moreover, an exogenously applied membrane-permeable peptide that competes for Tau-vesicle binding suppresses Tau-induced synaptic toxicity in rat neurons. Our work uncovers a presynaptic role of Tau that may be part of the early pathology in various Tauopathies and could be exploited therapeutically.||Notes:||Verstreken, P (reprint author), VIB KU Leuven Ctr Brain & Dis Res, B-3000 Leuven, Belgium. firstname.lastname@example.org||Keywords:||Alzheimer's disease; Tauopathies; Tau; presynaptic||Document URI:||http://hdl.handle.net/1942/23690||ISSN:||2041-1723||e-ISSN:||2041-1723||DOI:||10.1038/ncomms15295||ISI #:||000400962900001||Rights:||This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (c) The Author(s) 2017||Category:||A1||Type:||Journal Contribution||Validations:||ecoom 2018|
|Appears in Collections:||Research publications|
Show full item record
Files in This Item:
|Zhou et al_Dewachter_Verstreken_Nature Comms15295.pdf||Published version||3.69 MB||Adobe PDF||View/Open|
checked on Sep 2, 2020
WEB OF SCIENCETM
checked on May 21, 2022
checked on May 27, 2022
checked on May 27, 2022
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.