| First Author | Hyun DH | Year | 2010 |
| Journal | Exp Neurol | Volume | 225 |
| Issue | 2 | Pages | 423-9 |
| PubMed ID | 20673763 | Mgi Jnum | J:165298 |
| Mgi Id | MGI:4836804 | Doi | 10.1016/j.expneurol.2010.07.020 |
| Citation | Hyun DH, et al. (2010) The plasma membrane redox system is impaired by amyloid beta-peptide and in the hippocampus and cerebral cortex of 3xTgAD mice. Exp Neurol 225(2):423-9 |
| abstractText | Membrane-associated oxidative stress has been implicated in the synaptic dysfunction and neuronal degeneration that occurs in Alzheimer's disease (AD), but the underlying mechanisms are unknown. Enzymes of the plasma membrane redox system (PMRS) provide electrons for energy metabolism and recycling of antioxidants. Here, we show that activities of several PMRS enzymes are selectively decreased in plasma membranes from the hippocampus and cerebral cortex of 3xTgAD mice, an animal model of AD. Our results that indicate the decreased PMRS enzyme activities are associated with decreased levels of coenzyme Q(10) and increased levels of oxidative stress markers. Neurons overexpressing the PMRS enzymes (NQO1 or cytochrome b5 reductase) exhibit increased resistance to amyloid beta-peptide (Abeta). If and to what extent Abeta is the cause of the impaired PMRS enzymes in the 3xTgAD mice is unknown. Because these mice also express mutant tau and presenilin-1, it is possible that one or more of the PMRS could be adversely affected by these mutations. Nevertheless, the results of our cell culture studies clearly show that exposure of neurons to Abeta1-42 is sufficient to impair PMRS enzymes. The impairment of the PMRS in an animal model of AD, and the ability of PMRS enzyme activities to protect neurons against Abeta-toxicity, suggest enhancement PMRS function as a novel approach for protecting neurons against oxidative damage in AD and related disorders. |
