Neuronal subtype-specific metabolic changes in neurodegenerative and neuropsychiatric diseases predicted via a systems biology-based approach.

ABSTRACT: Understanding how distinct neuronal subtypes contribute to Alzheimer's disease (AD) pathology remains a major challenge. Patient-derived induced pluripotent stem cell (iPSC) studies have shown neuronal subtype-specific molecular and pathological signatures, yet the underlying metabolic shifts driving this selective vulnerability are not completely understood. Here we present iNeuron-GEM, the first manually curated, genome-scale metabolic network of human neurons that integrates transcriptomic and metabolic knowledge to resolve subtype-specific metabolic states. By coupling iNeuron-GEM with single nucleus RNA sequencing data from post-mortem human cohort studies, ROSMAP and SEA-AD, we capture neuronal subtype-specific metabolic features and fluxes and identify perturbations in lipid and ene

SUBMITTER: Jiang B 

PROVIDER: S-EPMC12637705 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature