Multi-omics reveal phosphatidic acid phosphatases modify Niemann-Pick type C disease severity - PubMed
3 hours ago
- #Lipid Metabolism
- #Neurodegeneration
- #Genetic Modifiers
- Niemann-Pick type C (NP-C) disease is a fatal neurodegenerative disorder caused by lysosomal lipid accumulation.
- Genetic, genomic, and lipidomic analyses across yeast, mice, and humans identified phosphatidic acid hydrolase (PAH1) as a key modifier affecting disease severity.
- Lipidomic profiling in Npc1 -/- mice showed dysregulation of triacylglycerol (TAG) metabolism correlates with disease progression.
- Deletion of PAH1 orthologues Lpin1 or Lpin2 in mice worsened symptoms, reducing lifespan and increasing lipid accumulation.
- LPIN3 variants in NP-C patients are linked to early childhood onset, highlighting lipins as disease modifiers.