The effects of different antioxidants on the activity of cerebrocortical MnSOD and Na,K-ATPase from post mortem Alzheimer's disease and age-matched normal brains

Curr Alzheimer Res. 2014 Jan;11(1):79-85. doi: 10.2174/15672050113106660179.

Abstract

Among the markers and targets of the early phase of Alzheimer's disease (AD) pathogenesis MnSOD (mitochondrial dysfunction) and Na-pump (disturbances in function/regulation) are often highlighted. This paper focused on comparison of the effects of three antioxidants on the activity of cerebrocortical MnSOD and Na,K-ATPase from post mortem Alzheimer's disease and age-matched normal brains. Antioxidant compounds with different origins: natural glutathione, synthetic UPF peptides (glutathione analogues) and phytoestrogen genistein were investigated. Firstly, MnSOD and Na,K-ATPase activities were found to be decreased in the post mortem AD brains compared with age-matched controls. Secondly, GSH had no effect on MnSOD activity, but decreased Na,K-ATPase activity both in the control and AD brains. Thirdly, UPF1 and UPF17 increased MnSOD activity, and UPF17 suppressed Na,K-ATPase activity. Further studies are needed to clarify, if the inhibitory effect of UPF17 on Na,K-ATPase could abolish the beneficial effect gained from MnSOD activation. Both the antioxidative potential of genistein and its potency to up-regulate Na,K-ATPase activity make it an attractive candidate substance to suppress the early phase of the pathogenesis of AD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / enzymology*
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Case-Control Studies
  • Frontal Lobe / drug effects*
  • Frontal Lobe / enzymology
  • Genistein / therapeutic use
  • Glutathione / analogs & derivatives
  • Glutathione / pharmacology
  • Glutathione / therapeutic use
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / enzymology
  • Oligopeptides / pharmacology
  • Oligopeptides / therapeutic use
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Superoxide Dismutase / metabolism*
  • Temporal Lobe / drug effects*
  • Temporal Lobe / enzymology

Substances

  • 4-methoxy-1-tyrosyl-gamma-glutamyl-cysteinyl-glycine
  • Antioxidants
  • Oligopeptides
  • Upf17 peptide
  • Genistein
  • Superoxide Dismutase
  • Sodium-Potassium-Exchanging ATPase
  • Glutathione