ArticleHuman molecular genetics2022
Reduced nuclear NAD+ drives DNA damage and subsequent immune activation in the retina.
Article in Human molecular genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Oxidative DNA damage drives apoptotic photoreceptor loss in NMNAT1-associated inherited retinal degeneration: a therapeutic opportunity.Cell death & disease · 2026Article
- RetiGene, a comprehensive gene atlas for inherited retinal diseases.American journal of human genetics · 2025Review
- Microglia dysfunction, neurovascular inflammation and focal neuropathologies are linked to IL-1- and IL-6-related systemic inflammation in COVID-19.Nature neuroscience · 2025Article
- Optimized Prime Editing of Human Induced Pluripotent Stem Cells to Efficiently Generate Isogenic Models of Mendelian Diseases.International journal of molecular sciences · 2024Article
- Advances in the role of the GADD45 family in neurodevelopmental, neurodegenerative, and neuropsychiatric disorders.Frontiers in neuroscience · 2024Review
- Activated SIRT1 contributes to DPT-induced glioma cell parthanatos by upregulation of NOX2 and NAT10.Acta pharmacologica Sinica · 2023Article
- NADMolecular biology reports · 2023Review
- Adipocyte NMNAT1 expression is essential for nuclear NADBiochemical and biophysical research communications · 2023Article
- Expression of NMNAT1 in the photoreceptors is sufficient to preventMolecular therapy. Methods & clinical development · 2023Article
- The role of epigenetic changes in the pathology and treatment of inherited retinal diseases.Frontiers in cell and developmental biology · 2023Review
- Endogenous metabolism in endothelial and immune cells generates most of the tissue vitamin B3 (nicotinamide).iScience · 2022Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in NMNAT1, a key enzyme involved in the synthesis of NAD+ in the nucleus, lead to an early onset severe inherited retinal degeneration (IRD). We aimed to understand the role of nuclear NAD+ in the retina and to identify the molecular mechanisms underlying NMNAT1-associated disease, using a mouse model that harbors the p.V9M mutation in Nmnat1 (Nmnat1V9M/V9M). We identified temporal transcriptional reprogramming in the retinas of Nmnat1V9M/V9M mice prior to retinal degeneration, which begins at 4 weeks of age, with no significant alterations in gene expression at 2 weeks of age and over 2600 differentially expressed genes by 3 weeks of age. Expression of the primary consumer of NAD+ in the nucleus, PARP1, an enzyme involved in DNA damage repair and transcriptional regulation, as well as 7 other PARP family enzymes, was elevated in the retinas of Nmnat1V9M/V9M. This was associated with elevated levels of DNA damage, PARP-mediated NAD+ consumption and migration of Iba1+/CD45+ microglia/macrophages to the subretinal space in the retinas of Nmnat1V9M/V9M mice. These findings suggest that photoreceptor cells are especially sensitive to perturbation of genome homeostasis, and that PARP-mediated cell death may play a role in other genetic forms of IRDs, and potentially other forms of neurodegeneration.
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Registered trials
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