In their recent article, Liu et al provided clear evidence that abnormal hyperphospharylation of tau protein may be induced by decreased 0-GlcNAcylation subsequent to a deficient glucose metabolism in Alzheimer disease (AD) brain. Experimentally, the authors damaged brain glucose metabolism by starvation for 48 hours, and this decreased 0-GlcNAcylation resulting in tau-protein hyperphosphorylation. Based on these results, the authors assumed that sporadic AD might be a metabolic brain disorder caused by abnormal cerebral glucose metabolism.
Some supplemental arguments may support this review.
During their processing from the immature to the mature state, proteins undergo modifications including 0-glycosylation and 0-GlcNAcylation. This process takes place in the endoplasmic reticulum (ER)/Golgi apparatus (GA) (1). The function of these intracellular compartments is ensured at a pH of 6 (2), the maintenance of which is ATP-dependent (3).
In sporadic AD brain, ATP formation has been found to be reduced in parallel to the severity of dementia (4) subsequent to decreased...