Increased neuronal glucose-6-phosphate dehydrogenase and sulfhydryl levels indicate reductive compensation to oxidative stress in Alzheimer disease.
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.
Russell
R L
RL
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Siedlak
S L
SL
Raina
A K
AK
Bautista
J M
JM
Smith
M A
MA
Perry
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003593:Cytoplasm / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D018384:Oxidative Stress; D010427:Pentose Phosphate Pathway; D017966:Pyramidal Cells / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D013438:Sulfhydryl Compounds; D005954:Glucosephosphate Dehydrogenase