Oxidation of KCNB1 channels in the human brain and in mouse model of Alzheimer's disease

Cell Death Dis. 2018 Jul 26;9(8):820. doi: 10.1038/s41419-018-0886-1.


Oxidative modification of the voltage-gated K+ channel subfamily B member 1 (KCNB1, Kv2.1) is emerging as a mechanism of neuronal vulnerability potentially capable of affecting multiple conditions associated with oxidative stress, from normal aging to neurodegenerative disease. In this study we report that oxidation of KCNB1 channels is exacerbated in the post mortem brains of Alzheimer's disease (AD) donors compared to age-matched controls. In addition, phosphorylation of Focal Adhesion kinases (FAK) and Src tyrosine kinases, two key signaling steps that follow KCNB1 oxidation, is also strengthened in AD vs. control brains. Quadruple transgenic mice expressing a non-oxidizable form of KCNB1 in the 3xTg-AD background (APPSWE, PS1M146V, and tauP301L), exhibit improved working memory along with reduced brain inflammation, protein carbonylation and intraneuronal β-amyloid (Aβ) compared to 3xTg-AD mice or mice expressing the wild type (WT) KCNB1 channel. We conclude that oxidation of KCNB1 channels is a mechanism of neuronal vulnerability that is pervasive in the vertebrate brain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged, 80 and over
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / prevention & control
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Brain / metabolism*
  • Dasatinib / therapeutic use
  • Disease Models, Animal
  • Female
  • Focal Adhesion Kinase 1 / metabolism
  • Gliosis
  • Humans
  • Male
  • Memory, Short-Term
  • Mice
  • Mice, Transgenic
  • Oxidative Stress
  • Protein Carbonylation
  • Shab Potassium Channels / chemistry
  • Shab Potassium Channels / genetics
  • Shab Potassium Channels / metabolism*
  • src-Family Kinases / metabolism


  • Amyloid beta-Peptides
  • KCNB1 protein, human
  • Shab Potassium Channels
  • Focal Adhesion Kinase 1
  • src-Family Kinases
  • Dasatinib