Phosphomannomutase 1

Phosphomannomutase 1 (PMM1) is a 29.7 kDa enzyme that catalyzes the synthesis of GDP-mannose and dolichol-phosphate-mannose, nucleotide-sugars required for mannosylation reactions critical to protein glycosylation and glycan biosynthesis (UniProt: Q92871). The protein may also participate in glucose-1,6-bisphosphate degradation under ischemic conditions in the brain. PMM1 is expressed in human tissues and plays a role in post-translational modification pathways essential for protein quality control and cell surface glycoprotein function.

In Alzheimer's Disease, PMM1 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). Quantitative proteomics analysis using TMT-labeled peptides and data-dependent acquisition across four subcellular fractions (P2, P3, S2, S3) demonstrated a mean log2 fold-change of −0.40, indicating reduced PMM1 levels in AD pathology. This downregulation of glycosylation machinery may reflect broader disruptions in protein synthesis and modification during neurodegeneration, potentially contributing to altered protein trafficking or accumulation of misfolded proteins characteristic of AD.