ArticleBrain : a journal of neurology2022
Raising cGMP restores proteasome function and myelination in mice with a proteotoxic neuropathy.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- The emerging role of ubiquitin-proteasome system dysfunction in the pathogenesis of perioperative neurocognitive disorders: a narrative review.Frontiers in behavioral neuroscience · 2026Review
- Regulation via compartmentation: adaptive localization of the proteasome under stress.Biochemical Society transactions · 2025Review
- Novel Dominant Splicing Variant in MPZ Associated With Unusual Charcot-Marie-Tooth Disease.Journal of the peripheral nervous system : JPNS · 2025Article
- Activation of XBP1s attenuates disease severity in models of proteotoxic Charcot-Marie-Tooth type 1B.Brain : a journal of neurology · 2025Article
- Unraveling the Role of Proteinopathies in Parasitic Infections.Biomedicines · 2025Review
- Promoting proteostasis by cAMP/PKA and cGMP/PKG.Trends in molecular medicine · 2025Review
- Activation of the 26S Proteasome to Reduce Proteotoxic Stress and Improve the Efficacy of PROTACs.ACS pharmacology & translational science · 2025Review
- Pharmacologically increasing cGMP improves proteostasis and reduces neuropathy in mouse models of CMT1.Cellular and molecular life sciences : CMLS · 2024Article
- Navigating the Landscape of CMT1B: Understanding Genetic Pathways, Disease Models, and Potential Therapeutic Approaches.International journal of molecular sciences · 2024Review
- Knockout of PA200 improves proteasomal degradation and myelination in a proteotoxic neuropathy.Life science alliance · 2024Article
- Activation of XBP1s attenuates disease severity in models of proteotoxic Charcot-Marie-Tooth type 1B.bioRxiv : the preprint server for biology · 2024Article
- Genetic blockade of the activation of 26S proteasomes by PKA is well tolerated by mice at baseline.American journal of cardiovascular disease · 2024Article
- Treatment with IFB-088 Improves Neuropathy in CMT1A and CMT1B Mice.Molecular neurobiology · 2022Article
Corrections and comments
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Authors and funding
6 authors.
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Abstract
Agents that raise cyclic guanosine monophosphate (cGMP) by activating protein kinase G increase 26S proteasome activities, protein ubiquitination and degradation of misfolded proteins. Therefore, they may be useful in treating neurodegenerative and other diseases caused by an accumulation of misfolded proteins. Mutations in myelin protein zero (MPZ) cause the peripheral neuropathy Charcot-Marie-Tooth type 1B (CMT1B). In peripheral nerves of a mouse model of CMT1B, where the mutant MPZS63del is expressed, proteasome activities are reduced, mutant MPZS63del and polyubiquitinated proteins accumulate and the unfolded protein response (p-eif2α) is induced. In HEK293 cells, raising cGMP stimulated ubiquitination and degradation of MPZS63del, but not of wild-type MPZ. Treating S63del mice with the phosphodiesterase 5 inhibitor, sildenafil-to raise cGMP-increased proteasome activity in sciatic nerves and reduced the levels of polyubiquitinated proteins, the proteasome reporter ubG76V-GFP and p-elF2α. Furthermore, sildenafil treatment reduced the number of amyelinated axons, and increased myelin thickness and nerve conduction velocity in sciatic nerves. Thus, agents that raise cGMP, including those widely used in medicine, may be useful therapies for CMT1B and other proteotoxic diseases.
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