ArticleNature communications2022
Compounds activating VCP D1 ATPase enhance both autophagic and proteasomal neurotoxic protein clearance.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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
28 citing papers in PubMed, 34 citations in OpenAlex.
- VCP at the crossroads of UPS and autophagy in cancer.Genes & diseases · 2027Review
- Canonical lymphocyte chemokine receptors CXCR3 and CXCR5 modulate neuronal autophagy.Cell death and differentiation · 2026Article
- FAF1 and FAF2 enhance unfolding by p97-UFD1-NPL4 complex enabling rational design of p97 activators.The EMBO journal · 2026Article
- Stimulating proteasomal degradation in human proteinopathies.The FEBS journal · 2026Review
- OsVPS34-generated PI3P recruits GPA5/Rab5a to regulate post-Golgi glutelin trafficking in rice endosperm.Plant physiology · 2026Article
- VCP modulation ameliorates pathological features in C9orf72 models.Cell death & disease · 2026Article
- Npl4 decodes polyubiquitin length and gates D1-D2 coupling in human VCP/p97.Research square · 2026Article
- Valosin-containing protein is cargo in Amyloid Precursor Protein extracellular vesicles.Cell communication and signaling : CCS · 2026Article
- Npl4 decodes polyubiquitin length and gates D1-D2 coupling in human VCP/p97.bioRxiv : the preprint server for biology · 2026Article
- Dual targeting of the UPS and autophagy as a novel therapy for neurodegenerative proteinopathies.Frontiers in cellular neuroscience · 2026Review
- Decoding protein dynamics with limited proteolysis coupled to mass spectrometry: A comprehensive review.Journal of pharmaceutical analysis · 2025Review
- Structural insights into the coupling between VCP, an essential unfoldase, and a deubiquitinase.The Journal of cell biology · 2025Article
- Palladium Nanoparticles Degrade Advanced Glycation End Products via Valosin-Containing Protein Mediated Autophagy to Attenuate High-Glucose/High-Fat-Induced Intervertebral Disc Degeneration.Exploration (Beijing, China) · 2025Article
- 2024 VCP International Conference: Exploring multi-disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein, to the therapeutic advancement for VCP-associated multisystem proteinopathy.Neurobiology of disease · 2025Review
- Hapalindole Q suppresses autophagosome-lysosome fusion by promoting YAP1 degradation via chaperon-mediated autophagy.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Nuclear proteasomes buffer cytoplasmic proteins during autophagy compromise.Nature cell biology · 2024Article
- The protein segregase VCP/p97 promotes host antifungal defense via regulation of SYK activation.PLoS pathogens · 2024Article
- Tau accumulation is cleared by the induced expression of VCP via autophagy.Acta neuropathologica · 2024Article
- Allosteric activation of VCP, an AAA unfoldase, by small molecule mimicry.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- International consensus guidelines for the definition, detection, and interpretation of autophagy-dependent ferroptosis.Autophagy · 2024Review
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 5 countries.
Funding
Abstract
Enhancing the removal of aggregate-prone toxic proteins is a rational therapeutic strategy for a number of neurodegenerative diseases, especially Huntington's disease and various spinocerebellar ataxias. Ideally, such approaches should preferentially clear the mutant/misfolded species, while having minimal impact on the stability of wild-type/normally-folded proteins. Furthermore, activation of both ubiquitin-proteasome and autophagy-lysosome routes may be advantageous, as this would allow effective clearance of both monomeric and oligomeric species, the latter which are inaccessible to the proteasome. Here we find that compounds that activate the D1 ATPase activity of VCP/p97 fulfill these requirements. Such effects are seen with small molecule VCP activators like SMER28, which activate autophagosome biogenesis by enhancing interactions of PI3K complex components to increase PI(3)P production, and also accelerate VCP-dependent proteasomal clearance of such substrates. Thus, this mode of VCP activation may be a very attractive target for many neurodegenerative diseases.
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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.