@article{f53308d33f5d4951ba57439d82989897,
title = "Increased G3BP2-Tau interaction in tauopathies is a natural defense against Tau aggregation",
abstract = "Many RNA-binding proteins (RBPs), particularly those associated with RNA granules, promote pathological protein aggregation in neurodegenerative diseases. Here, we demonstrate that G3BP2, a core component of stress granules, directly interacts with Tau and inhibits Tau aggregation. In the human brain, the interaction of G3BP2 and Tau is dramatically increased in multiple tauopathies, and it is independent of neurofibrillary tangle (NFT) formation in Alzheimer's disease (AD). Surprisingly, Tau pathology is significantly elevated upon loss of G3BP2 in human neurons and brain organoids. Moreover, we found that G3BP2 masks the microtubule-binding region (MTBR) of Tau, thereby inhibiting Tau aggregation. Our study defines a novel role for RBPs as a line of defense against Tau aggregation in tauopathies.",
keywords = "Alzheimer's disease, G3BP2, RBP, Tau aggregation, tauopathies",
author = "Congwei Wang and Marco Terrigno and Juan Li and Tania Distler and Pandya, {Nikhil J.} and Martin Ebeling and Stefka Tyanova and Hoozemans, {Jeroen J. M.} and Dijkstra, {Anke A.} and Luisa Fuchs and Shengqi Xiang and Azad Bonni and Fiona Gr{\"u}ninger and Ravi Jagasia",
note = "Funding Information: We thank L. Kulic, C. Di Primio, and G. Siano for discussions; S. Bae for graphic art assistance; and D. Calini and J. Messer for technical support. We thank the Roche postdoctoral fellowship program for funding C.W., M.T., and N.J.P. Experiments involving NMR were supported by the National Key R&D Program of China ( 2019YFA0508403 ) and National Natural Science Foundation of China ( 31971128 ). We thank the Strategic Priority Research Program of the Chinese Academy of Sciences grant ( XDB 37040202 ) for funding S.X. Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
month = sep,
day = "6",
doi = "https://doi.org/10.1016/j.neuron.2023.05.033",
language = "English",
volume = "111",
pages = "2660--2674.e9",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "17",
}