ArticleProceedings of the National Academy of Sciences of the United States of America2013
Proteasome overload is a common stress factor in multiple forms of inherited retinal degeneration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 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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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
77 citing papers in PubMed, 101 citations in OpenAlex.
- Article
- Article
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- Mechanisms that matter: unbiased cellular screening for degraders.npj drug discovery · 2025Review
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- The BBS/CCT chaperonin complex ensures the localization of the adhesion G protein-coupled receptor ADGRV1 to the base of primary cilia.Frontiers in cell and developmental biology · 2025Article
- Promotion of endoplasmic reticulum retrotranslocation by overexpression of E3 ubiquitin-protein ligase synoviolin 1 reduces endoplasmic reticulum stress and preserves cone photoreceptors in cyclic nucleotide-gated channel deficiency.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Progress in retinal and eye research · 2024Review
- Overexpression of Nfe2l1 increases proteasome activity and delays vision loss in a preclinical model of human blindness.Science advances · 2023Article
- PERK prevents rhodopsin degradation during retinitis pigmentosa by inhibiting IRE1-induced autophagy.The Journal of cell biology · 2023Article
- Regulation of germline proteostasis by HSF1 and insulin/IGF-1 signaling.Biochemical Society transactions · 2023Article
- Methods for In Vivo Characterization of Proteostasis in the Mouse Retina.Advances in experimental medicine and biology · 2023Article
- Extracellular vesicles highlight many cases of photoreceptor degeneration.Frontiers in molecular neuroscience · 2023Review
- Gene-agnostic approaches to treating inherited retinal degenerations.Frontiers in cell and developmental biology · 2023Review
- Network biology analysis of P23H rhodopsin interactome identifies protein and mRNA quality control mechanisms.Scientific reports · 2022Article
- Review
- Vitamin A Deficiency Alters the Phototransduction Machinery and Distinct Non-Vision-Specific Pathways in theBiomolecules · 2022Article
- Gene Therapy inHuman gene therapy · 2022Article
- Utility of the DHFR-based destabilizing domain across mouse models of retinal degeneration and aging.iScience · 2022Article
- Tsc2 knockout counteracts ubiquitin-proteasome system insufficiency and delays photoreceptor loss in retinitis pigmentosa.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Inherited retinal degenerations, caused by mutations in over 100 individual genes, affect approximately 2 million people worldwide. Many of the underlying mutations cause protein misfolding or mistargeting in affected photoreceptors. This places an increased burden on the protein folding and degradation machinery, which may trigger cell death. We analyzed how these cellular functions are affected in degenerating rods of the transducin γ-subunit (Gγ1) knockout mouse. These rods produce large amounts of transducin β-subunit (Gβ1), which cannot fold without Gγ1 and undergoes intracellular proteolysis instead of forming a transducin βγ-subunit complex. Our data revealed that the most critical pathobiological factor leading to photoreceptor cell death in these animals is insufficient capacity of proteasomes to process abnormally large amounts of misfolded protein. A decrease in the Gβ1 production in Gγ1 knockout rods resulted in a significant reduction in proteasomal overload and caused a striking reversal of photoreceptor degeneration. We further demonstrated that a similar proteasomal overload takes place in photoreceptors of other mutant mice where retinal degeneration has been ascribed to protein mistargeting or misfolding, but not in mice whose photoreceptor degenerate as a result of abnormal phototransduction. These results establish the prominence of proteasomal insufficiency across multiple degenerative diseases of the retina, thereby positioning proteasomes as a promising therapeutic target for treating these debilitating conditions.
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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.