6-phosphogluconolactonase

6-phosphogluconolactonase (PGLS) is a cytosolic enzyme that catalyzes the hydrolysis of 6-phosphogluconolactone to 6-phosphogluconate, a key step in the pentose phosphate pathway (UniProt: O95336). This metabolic enzyme participates in glucose catabolism and NADPH generation, which are critical for cellular redox homeostasis and biosynthetic reactions across tissues.

PGLS is ubiquitously expressed and involved in pentose phosphate pathway metabolism. No disease associations are documented in the UniProt record (UniProt: O95336). However, dysregulation of glucose metabolism and oxidative stress responses are relevant to neurodegenerative processes.

PGLS is significantly upregulated in post-mortem Alzheimer's disease brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.65 across subcellular fractions (Chaparral AD proteomics). This elevation suggests increased pentose phosphate pathway flux in AD brain, potentially reflecting enhanced demand for NADPH-dependent antioxidant defense or biosynthetic adaptation to metabolic stress in the disease state.