ArticleMolecular neurodegeneration2024
Urolithin A promotes p62-dependent lysophagy to prevent acute retinal neurodegeneration.
Article in Molecular neurodegeneration, 2024. 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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Who cites it
15 citing papers in PubMed.
- Mitophagy in neuronal health and disease: from mechanisms to neurodegeneration.The Journal of clinical investigation · 2026Review
- Sensory decline in aging and neurodegeneration: A mitochondrial perspective.Pharmacological research · 2026Review
- Functional Food-Derived Urolithins: Molecular Mechanisms, Health Effects, and Interactomics with Proteins and Extracellular Vesicles.Molecules (Basel, Switzerland) · 2026Review
- From homeostasis to pathology, organelle-specific autophagy in skeletal muscle: a PRISMA-ScR scoping review.Frontiers in physiology · 2026Review
- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- The key mechanisms and intervention strategies of cell-type-specific mitochondrial metabolism in ophthalmic diseases.Frontiers in cell and developmental biology · 2026Review
- Autophagy in ocular diseases: from mechanisms to therapeutic potential.Frontiers in cell and developmental biology · 2026Review
- Establishing PDE4 as a Novel Target of Urolithin-A in Mitigating LPS-induced Inflammation in Retinal Pigmented Epithelium Cells.Pharmaceutical research · 2025Article
- Urolithin Α modulates inter-organellar communication via calcium-dependent mitophagy to promote healthy ageing.Autophagy · 2025Article
- Intermittent fasting attenuates glial hyperactivation and photoreceptor degeneration in a NaIOCommunications biology · 2025Article
- Retinal Organoids: Innovative Tools for Understanding Retinal Degeneration.International journal of molecular sciences · 2025Review
- How crosstalk between mitochondria, lysosomes, and other organelles can prevent or promote dry age-related macular degeneration.Experimental eye research · 2025Review
- Recycling the recyclers: lysophagy emerges as a new pharmacological target for retinal degeneration.Autophagy · 2024Article
- Retinal G-protein-coupled receptor deletion exacerbates AMD-like changes via the PINK1-parkin pathway under oxidative stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Fast and quantitative mitophagy assessment by flow cytometry using theFrontiers in cell and developmental biology · 2024Article
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4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundAge-related macular degeneration (AMD) is the leading cause of blindness in elderly people in the developed world, and the number of people affected is expected to almost double by 2040. The retina presents one of the highest metabolic demands in our bodies that is partially or fully fulfilled by mitochondria in the neuroretina and retinal pigment epithelium (RPE), respectively. Together with its post-mitotic status and constant photooxidative damage from incoming light, the retina requires a tightly-regulated housekeeping system that involves autophagy. The natural polyphenol Urolithin A (UA) has shown neuroprotective benefits in several models of aging and age-associated disorders, mostly attributed to its ability to induce mitophagy and mitochondrial biogenesis. Sodium iodate (SI) administration recapitulates the late stages of AMD, including geographic atrophy and photoreceptor cell death.
methodsA combination of in vitro, ex vivo and in vivo models were used to test the neuroprotective potential of UA in the SI model. Functional assays (OCT, ERGs), cellular analysis (flow cytometry, qPCR) and fine confocal microscopy (immunohistochemistry, tandem selective autophagy reporters) helped address this question.
resultsUA alleviated neurodegeneration and preserved visual function in SI-treated mice. Simultaneously, we observed severe proteostasis defects upon SI damage induction, including autophagosome accumulation, that were resolved in animals that received UA. Treatment with UA restored autophagic flux and triggered PINK1/Parkin-dependent mitophagy, as previously reported in the literature. Autophagy blockage caused by SI was caused by severe lysosomal membrane permeabilization. While UA did not induce lysosomal biogenesis, it did restore upcycling of permeabilized lysosomes through lysophagy. Knockdown of the lysophagy adaptor SQSTM1/p62 abrogated viability rescue by UA in SI-treated cells, exacerbated lysosomal defects and inhibited lysophagy.
conclusionsCollectively, these data highlight a novel putative application of UA in the treatment of AMD whereby it bypasses lysosomal defects by promoting p62-dependent lysophagy to sustain proteostasis.
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