ReviewTranslational research : the journal of laboratory and clinical medicine2018
Aim for the core: suitability of the ubiquitin-independent 20S proteasome as a drug target in neurodegeneration.
Review in Translational research : the journal of laboratory and clinical medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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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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
36 citing papers in PubMed, 61 citations in OpenAlex.
- Human clearance systems have a layered architecture across tissues and cell types that supports varied proteome compositions.Autophagy · 2026Article
- Sex and Genotype Affect Mouse Hippocampal Gene Expression in Response to Blast-Induced Traumatic Brain Injury.Molecular neurobiology · 2025Article
- Proteasomal activation ameliorates neuronal phenotypes linked to FBXO11-deficiency.HGG advances · 2025Article
- Structural basis of human 20S proteasome biogenesis.Nature communications · 2024Article
- Advanced computational approaches to understand protein aggregation.Biophysics reviews · 2024Review
- Rpt5-Derived Analogs Stimulate Human Proteasome Activity in Cells and Degrade Proteins Forming Toxic Aggregates in Age-Related Diseases.International journal of molecular sciences · 2024Article
- Discovery and Development of Cyclic Peptide Proteasome Stimulators.Chembiochem : a European journal of chemical biology · 2024Article
- Protein Misfolding in Pregnancy: Current Insights, Potential Mechanisms, and Implications for the Pathogenesis of Preeclampsia.Molecules (Basel, Switzerland) · 2024Review
- Mechanisms of ubiquitin-independent proteasomal degradation and their roles in age-related neurodegenerative disease.Frontiers in cell and developmental biology · 2024Review
- The Ubiquitin Proteasome System as a Therapeutic Area in Parkinson's Disease.Neuromolecular medicine · 2023Review
- Protein degradation: expanding the toolbox to restrain cancer drug resistance.Journal of hematology & oncology · 2023Review
- Evaluation of quantitative biomarkers of aging in human PBMCs.Frontiers in aging · 2023Article
- Antioxidant Molecular Brain Changes Parallel Adaptive Cardiovascular Response to Forced Running in Mice.Antioxidants (Basel, Switzerland) · 2022Article
- Oleic amide derivatives as small molecule stimulators of the human proteasome's core particle.RSC medicinal chemistry · 2022Article
- The Proteasome Activator PA200/PSME4: An Emerging New Player in Health and Disease.Biomolecules · 2022Review
- Structural insights into the human PA28-20S proteasome enabled by efficient tagging and purification of endogenous proteins.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Stress routes clients to the proteasome via a BAG2 ubiquitin-independent degradation condensate.Nature communications · 2022Article
- The YΦ motif defines the structure-activity relationships of human 20S proteasome activators.Nature communications · 2022Article
- Carrying Excess Baggage Can Slowdown Life: Protein Clearance Machineries That Go Awry During Aging and the Relevance of Maintaining Them.Molecular neurobiology · 2022Review
- Nicotinamide phosphoribosyltransferase inhibitor ameliorates mouse aging-induced cognitive impairment.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Neurodegenerative diseases are a class of age-associated proteopathies characterized by the accumulation of misfolded and/or aggregation-prone proteins. This imbalance has been attributed, in part, to an age-dependent decay in the capacity of protein turnover. Most proteins are degraded by the ubiquitin-proteasome system (UPS), which is composed of ubiquitin ligases and regulatory particles, such as the 19S, that deliver cargo to the proteolytically active 20S proteasome (20S) core. However, a subset of clients, especially intrinsically disordered proteins (IDPs), are also removed by the action of the ubiquitin-independent proteasome system (UIPS). What are the specific contributions of the UPS and UIPS in the context of neurodegeneration? Here, we explore how age-associated changes in the relative contribution of the UPS and UIPS, combined with the IDP-like structure of many neurodegenerative disease-associated proteins, might contribute. Strikingly, the 20S has been shown to predominate in older neurons and to preferentially act on relevant substrates, such as synuclein and tau. Moreover, pharmacological activation of the 20S has been shown to accelerate removal of aggregation-prone proteins in some models. Together, these recent studies are turning attention to the 20S and the UIPS as potential therapeutic targets in neurodegeneration.
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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.