Increased Neuronal Glucose-6-phosphate Dehydrogenase and Sulfhydryl Levels Indicate Reductive Compensation to Oxidative Stress in Alzheimer Disease

• Published in: Archives of biochemistry and biophysics 1999-10, Vol.370 (2), p.236-239
• Main Authors: Russell, Robert L., Siedlak, Sandra L., Raina, Arun K., Bautista, José M., Smith, Mark A., Perry, George
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Alzheimer disease; Alzheimer Disease - enzymology; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Case-Control Studies; Child; Child, Preschool; Cytoplasm - metabolism; glucose-6-phosphate dehydrogenase; Glucosephosphate Dehydrogenase - metabolism; glutathione; Humans; Middle Aged; Oxidative Stress; Pentose Phosphate Pathway; Pyramidal Cells - enzymology; Pyramidal Cells - metabolism; Pyramidal Cells - pathology; redox control; Sulfhydryl Compounds - metabolism; sulfhydryls
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1006/abbi.1999.1404

We analyzed glucose-6-phosphate dehydrogenase, the rate-controlling enzyme of the pentose phosphate pathway and free sulfhydryls, to study redox balance in Alzheimer disease. Glucose-6-phosphate dehydrogenase plays a pivotal role in homeostatic redox control by providing reducing equivalents to glutathione, the major nonenzymatic cellular antioxidant. There is a multitude of evidence that marks oxidative stress proximally in the natural history of Alzheimer disease. Consistent with a role for glutathione in defense against increased reactive oxygen, we found an upregulation of glucose-6-phosphate dehydrogenase together with increased sulfhydryls in Alzheimer disease. These data indicate that reductive compensation may play an important role in combating oxidative stress in Alzheimer disease.