ArticleNeuron2025
Polyserine-mediated targeting of FAF2/UBXD8 ameliorates tau aggregation.
Article in Neuron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Faf2 is required for neural differentiation in embryonic neural progenitor cells.bioRxiv : the preprint server for biology · 2026Article
- Decoding the functions of nuclear speckles in neurodegeneration.Trends in neurosciences · 2026Review
- Nuclear tau aggregates inhibit RNA export and form by secondary seeding from cytosolic tau aggregates.bioRxiv : the preprint server for biology · 2026Article
- Polyserine domains are toxic and exacerbate tau pathology in mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Faf2 is required for neural differentiation in embryonic neural progenitor cells.Frontiers in cell and developmental biology · 2026Article
- From seeds to symptoms: the molecular landscape of tau seeding in Alzheimer's disease.Frontiers in neuroscience · 2026Review
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Authors and funding
6 authors.
Funding
Abstract
Tau aggregation is a hallmark of several neurodegenerative disorders, and the gain of toxic function of misfolded tau species is linked to pathobiology. Herein, we identified proteins that limit tau aggregation when targeted to tau aggregates by polyserine domains. Polyserine targeting was most effective at mitigating tau aggregation when fused to the vasolin-containing protein (VCP) adaptor protein fas-associated factor family member 2/UBX domain-containing protein 8 (FAF2/UBXD8). Surprisingly, FAF2/UBXD8 suppresses tau aggregation independent of VCP but does require ubiquitination, membrane localization, and a ubiquitin regulator X (UBX) domain. Validation in animal models demonstrated that polyserine-targeted FAF2/UBXD8 rescues tau-induced neurodegeneration in Drosophila. Further, delivery of targeted FAF2/UBXD8 reduced gliosis, seeding capacity, and insoluble tau levels in PS19 tau transgenic mice while improving contextual fear conditioning. Collectively, our findings highlight polyserine as a tau-targeting strategy and identify targeted FAF2/UBXD8 as a potent suppressor of tau pathology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.