ArticleHuman molecular genetics2017
Rescue of mutant rhodopsin traffic by metformin-induced AMPK activation accelerates photoreceptor degeneration.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 45 citations in OpenAlex.
- Metabolomics Effects of Folding Correction in Retinitis Pigmentosa Rhodopsin Mutant P23A.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Disease mechanisms revealed in the P23H opsin knock-in mouse model of retinitis pigmentosa.PNAS nexus · 2026Article
- The P23H Rhodopsin Mouse Model Reveals a Novel Interaction Between the Endoplasmic Reticulum and Connecting Cilium Rootlet Within Photoreceptors.Investigative ophthalmology & visual science · 2026Article
- Investigation of ABCA4 Missense Variants and Potential Small Molecule Rescue in Retinal Organoids.Investigative ophthalmology & visual science · 2025Article
- Metformin inhibits pathological retinal neovascularization but promotes retinal fibrosis in experimental neovascular age-related macular degeneration.Frontiers in pharmacology · 2025Article
- Article
- A Proximity Complementation Assay to Identify Small Molecules That Enhance the Traffic of ABCA4 Misfolding Variants.International journal of molecular sciences · 2024Article
- Molecular mechanisms underlying inherited photoreceptor degeneration as targets for therapeutic intervention.Frontiers in cellular neuroscience · 2024Review
- Pathomechanisms of Inherited Retinal Degeneration and Perspectives for Neuroprotection.Cold Spring Harbor perspectives in medicine · 2023Review
- The Effect of Calorie Restriction on Protein Quality Control in Yeast.Biomolecules · 2023Review
- CaFrontiers in cell and developmental biology · 2023Article
- Old drug, new tricks: the utility of metformin in infection and vaccination responses to influenza and SARS-CoV-2 in older adults.Frontiers in aging · 2023Review
- Rhodopsin-associated retinal dystrophy: Disease mechanisms and therapeutic strategies.Frontiers in neuroscience · 2023Review
- Cardio-respiratory and phenotypic rescue of dystrophin/utrophin-deficient mice by combination therapy.EMBO reports · 2022Article
- Article
- Cellular stress signaling and the unfolded protein response in retinal degeneration: mechanisms and therapeutic implications.Molecular neurodegeneration · 2022Review
- Metformin and retinal diseases in preclinical and clinical studies: Insights and review of literature.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- Beyond Genetics: The Role of Metabolism in Photoreceptor Survival, Development and Repair.Frontiers in cell and developmental biology · 2022Review
- Review
- Pharmacological Inhibition of the VCP/Proteasome Axis Rescues Photoreceptor Degeneration in RHOBiomolecules · 2021Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Protein misfolding caused by inherited mutations leads to loss of protein function and potentially toxic 'gain of function', such as the dominant P23H rhodopsin mutation that causes retinitis pigmentosa (RP). Here, we tested whether the AMPK activator metformin could affect the P23H rhodopsin synthesis and folding. In cell models, metformin treatment improved P23H rhodopsin folding and traffic. In animal models of P23H RP, metformin treatment successfully enhanced P23H traffic to the rod outer segment, but this led to reduced photoreceptor function and increased photoreceptor cell death. The metformin-rescued P23H rhodopsin was still intrinsically unstable and led to increased structural instability of the rod outer segments. These data suggest that improving the traffic of misfolding rhodopsin mutants is unlikely to be a practical therapy, because of their intrinsic instability and long half-life in the outer segment, but also highlights the potential of altering translation through AMPK to improve protein function in other protein misfolding diseases.
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Registered trials
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