ArticleeLife2022
Pathway-specific effects of ADSL deficiency on neurodevelopment.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Allopurinol Treatment Improves Cognitive Skills, Adaptive Behavior, and Biochemical Markers in Young Patients With Adenylosuccinate Lyase Deficiency.Journal of inherited metabolic disease · 2025Trial
- MECP2 Duplication Uncouples Mitochondrial and Purine Metabolism During neuronal maturation.bioRxiv : the preprint server for biology · 2025Article
- Metabolic functions for molecular chaperones and stress proteins in microcephaly.Cellular and molecular life sciences : CMLS · 2025Review
- Adenylosuccinate lyase (ADSL) is a pan-cancer prognostic and immune biomarker with distinct roles in hepatocellular carcinoma.Discover oncology · 2025Article
- Development of Cell-Permeable Adenylosuccinate Lyase Inhibitor.Methods and protocols · 2025Article
- Emerging role of complement system in the induction of neuroinflammation in adenylosuccinate lyase deficiency disorder.Brain, behavior, & immunity - health · 2025Review
- ADSL deficiency is a secondary mitochondrial disease affecting organelle homeostasis and ERK2/AKT signaling in a linear genotype-phenotype relation.Cell reports · 2025Article
- Purine Metabolism and Dystonia: Perspectives of a Long-Promised Relationship.Annals of neurology · 2025Review
- Notch2 Signaling Drives Cardiac Hypertrophy by Suppressing Purine Nucleotide Metabolism.Research (Washington, D.C.) · 2025Article
- Roles of nucleotide metabolism in pancreatic cancer.Frontiers in immunology · 2025Review
- Case Report: Adenylosuccinate lyase deficiency type I caused by splicing disruption due to a novel missense variant in theFrontiers in genetics · 2025Article
- Purinosomes and Purine Metabolism in Mammalian Neural Development: A Review.Acta histochemica et cytochemica · 2024Review
- Mesenchymal Stem Cells and Purinergic Signaling in Autism Spectrum Disorder: Bridging the Gap between Cell-Based Strategies and Neuro-Immune Modulation.Biomedicines · 2024Review
- A Caenorhabditis elegans model of adenylosuccinate lyase deficiency reveals neuromuscular and reproductive phenotypes of distinct etiology.Molecular genetics and metabolism · 2023Article
- Spatiotemporal Regulation ofeNeuro · 2023Article
- Article
- Adenylosuccinate lyase deficiency affects neurobehavior via perturbations to tyramine signaling in Caenorhabditis elegans.PLoS genetics · 2023Article
- Inborn Errors of Purine Salvage and Catabolism.Metabolites · 2023Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 5 countries.
Funding
Abstract
Adenylosuccinate lyase (ADSL) functions in de novo purine synthesis (DNPS) and the purine nucleotide cycle. ADSL deficiency (ADSLD) causes numerous neurodevelopmental pathologies, including microcephaly and autism spectrum disorder. ADSLD patients have normal serum purine nucleotide levels but exhibit accumulation of dephosphorylated ADSL substrates, S-Ado, and SAICAr, the latter being implicated in neurotoxic effects through unknown mechanisms. We examined the phenotypic effects of ADSL depletion in human cells and their relation to phenotypic outcomes. Using specific interventions to compensate for reduced purine levels or modulate SAICAr accumulation, we found that diminished AMP levels resulted in increased DNA damage signaling and cell cycle delays, while primary ciliogenesis was impaired specifically by loss of ADSL or administration of SAICAr. ADSL-deficient chicken and zebrafish embryos displayed impaired neurogenesis and microcephaly. Neuroprogenitor attrition in zebrafish embryos was rescued by pharmacological inhibition of DNPS, but not increased nucleotide concentration. Zebrafish also displayed phenotypes commonly linked to ciliopathies. Our results suggest that both reduced purine levels and impaired DNPS contribute to neurodevelopmental pathology in ADSLD and that defective ciliogenesis may influence the ADSLD phenotypic spectrum.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.