AI Article Synopsis
- RNA-binding proteins (RBPs), especially those in RNA granules, are linked to protein aggregation issues in neurodegenerative diseases, particularly involving the protein Tau.* -
- G3BP2, a crucial part of stress granules, directly interacts with Tau, inhibiting its aggregation and showing increased interaction in various tau-related diseases, independent of neurofibrillary tangle formation in Alzheimer's.* -
- The absence of G3BP2 in human neurons leads to increased Tau pathology, as G3BP2 effectively masks Tau's microtubule-binding region, highlighting the protective role of RBPs against Tau aggregation in tauopathies.*
Article 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.
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| http://dx.doi.org/10.1016/j.neuron.2023.05.033 | DOI Listing |
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