ArticleScience advances2022
Numb regulates Tau levels and prevents neurodegeneration in tauopathy mouse models.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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
11 citing papers in PubMed, 16 citations in OpenAlex.
- MicroRNA-6833-3p drives prostate cancer progression and stemness by targeting the NUMB-mediated NOTCH signaling pathway.Cell cycle (Georgetown, Tex.) · 2026Article
- Functional Analysis of Late-Onset Alzheimer's Disease Risk Genes inbioRxiv : the preprint server for biology · 2026Article
- Modeling neurodegeneration in the retina and strategies for developing pan-neurodegenerative therapies.Molecular neurodegeneration · 2025Review
- Article
- Morphological and Molecular Profiling of Amyloid-β Species in Alzheimer's Pathogenesis.Molecular neurobiology · 2025Review
- The Deubiquitinase USP2 Modulates Photic Entrainment of the Circadian Clock at the Level of the Suprachiasmatic Nucleus.Journal of neurochemistry · 2025Article
- Transgenic sensors reveal compartment-specific effects of aggregation-prone proteins on subcellular proteostasis during aging.Cell reports methods · 2024Article
- Identification of high-performing antibodies for the reliable detection of Tau proteoforms by Western blotting and immunohistochemistry.Acta neuropathologica · 2024Article
- Review
- NUMB72 - a therapeutic target for tauopathies?Nature reviews. Neurology · 2022Article
- Retinal manifestations and their diagnostic significance in Alzheimer's disease.Journal of Alzheimer's disease reportsReview
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulation of the microtubule-associated protein Tau is linked to neuronal cell death in tauopathies, but how intraneuronal Tau levels are regulated in health and disease remains unclear. Here, we show that conditional inactivation of the trafficking adaptor protein Numb in retinal ganglion cells (RGCs) increases Tau levels and leads to axonal blebbing, which is followed by neuronal cell loss in aged mice. In the TauP301S mouse model of tauopathy, conditional inactivation of Numb in RGCs and spinal motoneurons accelerates neurodegeneration, and loss of Numb in motoneurons also leads to precocious hindlimb paralysis. Conversely, overexpression of the long isoform of Numb (Numb-72) decreases intracellular Tau levels and reduces axonal blebbing in TauP301S RGCs, leading to improved electrical activity in cultured neurons and improves performance in a visually guided behavior test in vivo. These results uncover Numb as a key regulator of intracellular Tau levels and identify Numb-72 as a potential therapeutic factor for tauopathies.
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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.