NMN-rescued gene pathways compared with schizophrenia and clozapine-proxied treatment resistance
In this abstract, 35 NMN-rescued mouse genes mapped to 10 pathways showed strong directional concordance with schizophrenia and clozapine-proxied treatment-resistant schizophrenia genetic profiles; fatty acid degradation was the strongest shared signal. This is genetic overlap analysis, not evidence of human benefit. [1]
Automatic summary · not editorially reviewed
The key findings
Thirty-five robust NMN-rescued genes from a mouse dataset re-analysis were mapped to 10 KEGG pathways. [1]
Schizophrenia and clozapine-proxied treatment-resistant schizophrenia showed directional concordance across all 10 pathways, with Pearson correlations of 0.75 to 0.88. [1]
Fatty acid degradation was the strongest shared signal, with a CPT2-centered gene-level profile. [1]
The source at a glance
- Study type / format
- Abstract of a genetic overlap and pathway enrichment analysis
- Population / context
- Genes from a mouse NMN dataset compared with human schizophrenia and clozapine-proxied treatment-resistant schizophrenia genetic profiles
- Summary based on
- Study abstract
- Publication status
- Preprint · peer-review status not confirmed
- Original publication
- August 5, 2026
NMN-rescued mouse genes mapped to ten pathways
The authors took 35 robust NMN-rescued genes from a re-analysis of the Mills NMN dataset in mice and mapped them to 10 KEGG pathways. These included fatty acid degradation, endocytosis, MAPK and Ras signaling, PPAR signaling, autophagy, regulation of actin cytoskeleton, citrate cycle-related metabolism, neuroactive ligand-receptor interaction and synaptic vesicle cycle. They then compared gene-level genetic profiles for schizophrenia and for treatment-resistant schizophrenia, the latter proxied by clozapine exposure.
Supporting source [1]
Strong concordance; fatty acid degradation strongest shared signal
Across all 10 pathways, schizophrenia and clozapine-proxied treatment-resistant schizophrenia showed strong directional concordance, with Pearson correlations from 0.75 to 0.88. No pathway showed significant pathway-level separation between the two. Fatty acid degradation was the strongest shared signal, with the highest Stouffer Z in both and a CPT2-centered gene-level profile. Autophagy differed: pathway-level effects did not define treatment resistance, but leave-one-out analysis found marked influence from ATG13, RPTOR, TAX1BP1, CALCOCO2, PIK3R4, MAP1LC3A, AKT3, SNAP29, RHEB, AMBRA1 and GABARAP. MAPK3 was the most recurrent high-influence driver across pathways.
Supporting source [1]
Genetic overlap only; abstract scope and mouse-derived genes
The authors conclude that NMN-responsive transcriptional programs appear to overlap with core schizophrenia biology through shared metabolic and cellular homeostasis pathways. They name CPT2-linked fatty acid oxidation and gene-level autophagy or mTOR-related nodes as the strongest translational leads and call for future work on NAD⁺-linked metabolic stratification, autophagy burden and adjunctive interventions. These are proposed directions, not tested treatments. The NMN-rescued genes came from mouse data, and the treatment-resistance group was defined by clozapine exposure as a proxy.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. The NMN-rescued genes derive from mouse data, treatment-resistant schizophrenia is proxied by clozapine exposure, and the work reports genetic profile overlap, not human outcomes or treatment effects. Proposed future directions are not validated interventions.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Cheung N. · europepmc.org · August 5, 2026