ArticleHuman molecular genetics2018
Transcriptome and functional analysis in a Drosophila model of NGLY1 deficiency provides insight into therapeutic approaches.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 64 citations in OpenAlex.
- Impacts of N-glycanase1 (NGLY1) Down Regulation on the Function of Mitochondria.Journal of cellular biochemistry · 2026Article
- Natural SEL1L variants rescue a model of NGLY1 deficiency and modify ERAD function and proteasome sensitivity.PLoS genetics · 2025Article
- Increased oxidative stress and autophagy in NGLY1 patient iPSC-derived neural stem cells.Experimental cell research · 2025Article
- Nrf1 acts as a highly-conserved determinon for maintaining robust redox homeostasis in the eco-evo-devo process of life histories.Cell stress · 2025Review
- Systemic gene therapy corrects the neurological phenotype in a mouse model of NGLY1 deficiency.JCI insight · 2024Article
- Mutations in nucleotide metabolism genes bypass proteasome defects in png-1/NGLY1-deficient Caenorhabditis elegans.PLoS biology · 2024Article
- Gut barrier defects, intestinal immune hyperactivation and enhanced lipid catabolism drive lethality in NGLY1-deficient Drosophila.Nature communications · 2023Article
- Role of NFE2L1 in the Regulation of Proteostasis: Implications for Aging and Neurodegenerative Diseases.Biology · 2023Review
- N-glycoproteomics reveals distinct glycosylation alterations in NGLY1-deficient patient-derived dermal fibroblasts.Journal of inherited metabolic disease · 2023Article
- Generation and characterization of NGLY1 patient-derived midbrain organoids.Frontiers in cell and developmental biology · 2023Article
- Chemical Therapies for Congenital Disorders of Glycosylation.ACS chemical biology · 2022Review
- An in vivo drug repurposing screen and transcriptional analyses reveals the serotonin pathway and GSK3 as major therapeutic targets for NGLY1 deficiency.PLoS genetics · 2022Article
- Off-target inhibition of NGLY1 by the polycaspase inhibitor Z-VAD-fmk induces cellular autophagy.The FEBS journal · 2022Article
- Comprehensive Analysis of the Structure and Function of Peptide:N-Glycanase 1 and Relationship with Congenital Disorder of Deglycosylation.Nutrients · 2022Review
- NGLY1 Deficiency, a Congenital Disorder of Deglycosylation: From Disease Gene Function to Pathophysiology.Cells · 2022Review
- Deficiency of N-glycanase 1 perturbs neurogenesis and cerebral development modeled by human organoids.Cell death & disease · 2022Article
- Ferroptosis regulation by the NGLY1/NFE2L1 pathway.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Cytosolic O-GlcNAcylation and PNG1 maintain Drosophila gut homeostasis by regulating proliferation and apoptosis.PLoS genetics · 2022Article
- Tracing the NGLY1 footprints: insights from Drosophila.Journal of biochemistry · 2022Review
- Why rare disease needs precision medicine-and precision medicine needs rare disease.Cell reports. Medicine · 2022Article
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
Autosomal recessive loss-of-function mutations in N-glycanase 1 (NGLY1) cause NGLY1 deficiency, the only known human disease of deglycosylation. Patients present with developmental delay, movement disorder, seizures, liver dysfunction and alacrima. NGLY1 is a conserved cytoplasmic component of the Endoplasmic Reticulum Associated Degradation (ERAD) pathway. ERAD clears misfolded proteins from the ER lumen. However, it is unclear how loss of NGLY1 function impacts ERAD and other cellular processes and results in the constellation of problems associated with NGLY1 deficiency. To understand how loss of NGLY1 contributes to disease, we developed a Drosophila model of NGLY1 deficiency. Loss of NGLY1 function resulted in developmental delay and lethality. We used RNAseq to determine which processes are misregulated in the absence of NGLY1. Transcriptome analysis showed no evidence of ER stress upon NGLY1 knockdown. However, loss of NGLY1 resulted in a strong signature of NRF1 dysfunction among downregulated genes, as evidenced by an enrichment of genes encoding proteasome components and proteins involved in oxidation-reduction. A number of transcriptome changes also suggested potential therapeutic interventions, including dysregulation of GlcNAc synthesis and upregulation of the heat shock response. We show that increasing the function of both pathways rescues lethality. Together, transcriptome analysis in a Drosophila model of NGLY1 deficiency provides insight into potential therapeutic approaches.
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