ArticleHuman molecular genetics2017
Enhanced tau pathology via RanBP9 and Hsp90/Hsc70 chaperone complexes.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 57 citations in OpenAlex.
- Synaptic Chaperone Dysfunction as a Convergent Mechanism in Neurodegenerative and Psychiatric Disorders.Neuroscience insights · 2026Review
- The interactome of tau phosphorylated at T217 in Alzheimer's disease human brain tissue.Acta neuropathologica · 2025Article
- An in vivo "turning model" reveals new RanBP9 interactions in lung macrophages.Cell death discovery · 2025Article
- The role of small GTPases in Alzheimer's disease tau pathologies.Frontiers in cellular neuroscience · 2025Review
- The role of the FKBP51-Hsp90 complex in Alzheimer's disease: An emerging new drug target.Cell stress & chaperones · 2024Review
- A single-nuclei paired multiomic analysis of the human midbrain reveals age- and Parkinson's disease-associated glial changes.Nature aging · 2024Article
- Identification of immunogenic cell death-related genes involved in Alzheimer's disease.Scientific reports · 2024Article
- DnaJs are enriched in tau regulators.International journal of biological macromolecules · 2023Article
- Energy Crisis Links to Autophagy and Ferroptosis in Alzheimer's Disease: Current Evidence and Future Avenues.Current neuropharmacology · 2023Article
- Article
- Modulation of synaptic plasticity, motor unit physiology, and TDP-43 pathology by CHCHD10.Acta neuropathologica communications · 2022Article
- Structural and Functional Insights into GID/CTLH E3 Ligase Complexes.International journal of molecular sciences · 2022Review
- β-arrestin1 promotes tauopathy by transducing GPCR signaling, disrupting microtubules and autophagy.Life science alliance · 2022Article
- SSH1 impedes SQSTM1/p62 flux and MAPT/Tau clearance independent of CFL (cofilin) activation.Autophagy · 2021Article
- Proteomic analysis of ubiquitination substrates reveals a CTLH E3 ligase complex-dependent regulation of glycolysis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Inhibition of 2-Arachidonoylglycerol Metabolism Alleviates Neuropathology and Improves Cognitive Function in a Tau Mouse Model of Alzheimer's Disease.Molecular neurobiology · 2021Article
- Article
- Pharmacological Modulators of Tau Aggregation and Spreading.Brain sciences · 2020Review
- CHCHD10-regulated OPA1-mitofilin complex mediates TDP-43-induced mitochondrial phenotypes associated with frontotemporal dementia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- β-Arrestin2 oligomers impair the clearance of pathological tau and increase tau aggregates.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Accumulation of amyloid β (Aβ) and tau represent the two major pathological hallmarks of Alzheimer's disease (AD). Despite the critical importance of Aβ accumulation as an early event in AD pathogenesis, multiple lines of evidence indicate that tau is required to mediate Aβ-induced neurotoxic signals in neurons. We have previously shown that the scaffolding protein Ran-binding protein 9 (RanBP9), which is highly elevated in brains of AD and AD mouse models, both enhances Aβ production and mediates Aβ-induced neurotoxicity. However, it is unknown whether and how RanBP9 transmits Aβ-induced neurotoxic signals to tau. Here we show for the first time that overexpression or knockdown of RanBP9 directly enhances and reduces tau levels, respectively, in vitro and in vivo. Such changes in tau levels are associated with the ability of RanBP9 to physically interact with tau and heat shock protein 90/heat shock cognate 70 (Hsp90/Hsc70) complexes. Meanwhile, both RanBP9 and tau levels are simultaneously reduced by Hsp90 or Hsc70 inhibitors, whereas overexpression or knockdown of RanBP9 significantly diminishes the anti-tau potency of Hsp90/Hsc70 inhibitors as well as Hsc70 variants (WT & E175S). Further, RanBP9 increases the capacity for Hsp90 and Hsc70 complexes to bind ATP and enhances their ATPase activities in vitro. These observations in vitro and cell lines are recapitulated in primary neurons and in vivo, as genetic reduction in RanBP9 not only ameliorates tauopathy in Tau-P301S mice but also rescues the deficits in synaptic integrity and plasticity.
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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.