ArticleScience (New York, N.Y.)2024
Aggregate-selective removal of pathological tau by clustering-activated degraders.
Article in Science (New York, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed.
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Divergent Roles of mGlu2 and mGlu3 Receptors in Amyloid-β Production and Cognitive Dysfunctions in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Redirecting TRIM21 with TRIMTACs for the targeted degradation of multimeric proteins.The FEBS journal · 2026Review
- Programmable aging function-related mitochondrial DNA 5-methylcytosine (m5C) modification with a TALE-directed methyltransferase.Cell communication and signaling : CCS · 2026Article
- New Discoveries in the Field of Neuropharmacology.Biomolecules · 2026Article
- TRIM21 induces selective autophagy of viruses and bacteria.Molecular cell · 2026Article
- The molecular basis for nuclear pore destruction by a proximity-inducing molecular glue.Cell chemical biology · 2026Article
- Design principles for optogenetic-based targeted protein degradation.Synthetic and systems biotechnology · 2026Review
- Ionizable Polymeric Micelles Targeting Transferrin Receptor 1 Enhance Systemic mRNA Delivery to the Brain.Molecular pharmaceutics · 2026Article
- Tracking tau and cellular responses in human iPSC-microglia: from uptake to seedable secretion, including in extracellular vesicles.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- PML targets and resolves structured protein inclusions to mitigate neurodegeneration.Nature cell biology · 2026Article
- Degrons and degradation signals beyond short linear motifs.Nature chemical biology · 2026Review
- Advances in controllable targeted protein degradation: emerging strategies and mechanisms.Science China. Life sciences · 2026Review
- Reliable repurposing of the antibody interactome inside the cell.Nature communications · 2026Article
- Identification of the E3 ligase TRIM21 as a crucial regulator of STAT1 in metabolic dysfunction-associated steatohepatitis.Cell communication and signaling : CCS · 2026Article
- Nanobodies in biomedicine: from molecular characteristics to fabrication and clinical translation.Military Medical Research · 2026Review
- Dual targeting of the UPS and autophagy as a novel therapy for neurodegenerative proteinopathies.Frontiers in cellular neuroscience · 2026Review
- Steps toward developing an algorithm to facilitate recognition of translational science.Journal of clinical and translational science · 2026Article
- Amelioration of Alzheimer's Disease Pathology in Zebrafish by Photobiomodulation.Biomedicines · 2025Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Selective degradation of pathological protein aggregates while sparing monomeric forms is of major therapeutic interest. The E3 ligase tripartite motif-containing protein 21 (TRIM21) degrades antibody-bound proteins in an assembly state-specific manner due to the requirement of TRIM21 RING domain clustering for activation, yet effective targeting of intracellular assemblies remains challenging. Here, we fused the RING domain of TRIM21 to a target-specific nanobody to create intracellularly expressed constructs capable of selectively degrading assembled proteins. We evaluated this approach against green fluorescent protein-tagged histone 2B (H2B-GFP) and tau, a protein that undergoes pathological aggregation in Alzheimer's and other neurodegenerative diseases. RING-nanobody degraders prevented or reversed tau aggregation in culture and in vivo, with minimal impact on monomeric tau. This approach may have therapeutic potential for the many disorders driven by intracellular protein aggregation.
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What OpenQuestion holds
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.