Pathologic tau–stress granule interaction (Tau–SG interaction)

The pathologic tau–stress granule interaction refers to the association between the microtubule-associated protein tau (MAPT) and cytoplasmic stress granules (SGs), which are transient ribonucleoprotein complexes formed during cellular stress (Wolozin & Ivanov, 2019). In neurodegenerative diseases known as tauopathies, such as Alzheimer's disease, tau becomes hyperphosphorylated and misfolded, leading to its recruitment into SGs (Vanderweyde et al., 2016). This interaction is believed to facilitate the nucleation of tau into toxic oligomers and insoluble fibrils, thereby driving disease progression (Ash et al., 2014). Key SG proteins like TIA-1 and G3BP1 have been shown to physically interact with tau and promote its liquid-liquid phase separation and subsequent aggregation (Apicco et al., 2018; Zhang et al., 2020). Therapeutic strategies targeting this interaction aim to disrupt the recruitment of tau to SGs or modulate SG dynamics to prevent the formation of pathological tau species. Research in this area focuses on small molecules and antisense oligonucleotides that can selectively interfere with these protein-protein interactions without compromising the cell's essential stress response mechanisms (Apicco et al., 2018).

Other names

Tau-stress granule associationTau-RNP complexTau-TIA1 interactionTau-G3BP1 interactionTau-stress granule complex

Disruption of the physical association between pathologic tau and stress granule nucleating proteins (e.g., TIA-1, G3BP1) to inhibit tau aggregation and neurotoxicity.