ArticleFree radical biology & medicine2010
Selective vulnerability of neurons to acute toxicity after proteasome inhibitor treatment: implications for oxidative stress and insolubility of newly synthesized proteins.
Article in Free radical biology & medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 24 citations in OpenAlex.
- Tau Disaggregation by a CNS-Permeable Small Molecule Reduces Fibril and Oligomer Burden and Preserves Proteostasis and Behavior.bioRxiv : the preprint server for biology · 2026Article
- Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A Practical Review of Proteasome Pharmacology.Pharmacological reviews · 2019Review
- NGF-Dependent Changes in Ubiquitin Homeostasis Trigger Early Cholinergic Degeneration in Cellular and Animal AD-Model.Frontiers in cellular neuroscience · 2018Article
- The Proteasome Inhibition Model of Parkinson's Disease.Journal of Parkinson's disease · 2017Review
- The Ubiquitin-Proteasome System: Potential Therapeutic Targets for Alzheimer's Disease and Spinal Cord Injury.Frontiers in molecular neuroscience · 2016Review
- Morphological Changes within the Rat Lateral Ventricle after the Administration of Proteasome Inhibitors.PloS one · 2015Article
- Negative regulation of 26S proteasome stability via calpain-mediated cleavage of Rpn10 subunit upon mitochondrial dysfunction in neurons.The Journal of biological chemistry · 2013Article
- Overexpression of Atg5 in mice activates autophagy and extends lifespan.Nature communications · 2013Article
- cAMP stimulates the ubiquitin/proteasome pathway in rat spinal cord neurons.Neuroscience letters · 2012Article
- Article
- Proteasome alterations during adipose differentiation and aging: links to impaired adipocyte differentiation and development of oxidative stress.Free radical biology & medicine · 2011Article
- Aging is associated with hypoxia and oxidative stress in adipose tissue: implications for adipose function.American journal of physiology. Endocrinology and metabolism · 2011Article
- Amino acid analog toxicity in primary rat neuronal and astrocyte cultures: implications for protein misfolding and TDP-43 regulation.Journal of neuroscience research · 2011Article
- Walking the oxidative stress tightrope: a perspective from the naked mole-rat, the longest-living rodent.Current pharmaceutical design · 2011Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Maintaining protein homeostasis is vital to cell viability, with numerous studies demonstrating a role for proteasome inhibition occurring during the aging of a variety of tissues and, presumably, contributing to the disruption of cellular homeostasis during aging. In this study we sought to elucidate the differences between neurons and astrocytes in regard to basal levels of protein synthesis, proteasome-mediated protein degradation, and sensitivity to cytotoxicity after proteasome inhibitor treatment. In these studies we demonstrate that neurons have an increased vulnerability, compared to astrocyte cultures, to proteasome-inhibitor-induced cytotoxicity. No significant difference was observed between these two cell types in regard to the basal rates of protein synthesis, or basal rates of protein degradation, in the pool of short-lived proteins. After proteasome inhibitor treatment neuronal crude lysates were observed to undergo greater increases in the levels of ubiquitinated and oxidized proteins and selectively exhibited increased levels of newly synthesized proteins accumulating within the insoluble protein pool, compared to astrocytes. Together, these data suggest a role for increased oxidized proteins and sequestration of newly synthesized proteins in the insoluble protein pool, as potential mediators of the selective neurotoxicity after proteasome inhibitor treatment. The implications for neurons exhibiting increased sensitivity to acute proteasome inhibitor exposure, and the corresponding changes in protein homeostasis observed after proteasome inhibition, are discussed in the context of both aging and age-related disorders of the nervous system.
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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.