Nrf2 and DJ1 are consistently upregulated in inflammatory multiple sclerosis lesions

Free Radic Biol Med. 2010 Nov 1;49(8):1283-9. doi: 10.1016/j.freeradbiomed.2010.07.013. Epub 2010 Jul 29.


Oxidative stress plays a major role in multiple sclerosis (MS), a chronic inflammatory central nervous system (CNS) disease. Invading leukocytes contribute to cell damage and demyelination by producing excessive amounts of cytotoxic mediators, including reactive oxygen species (ROS). To counteract the damaging effects of ROS the CNS is endowed with a repertoire of endogenous antioxidant enzymes, which are regulated by the transcription factor NF-E2-related factor 2 (Nrf2). Upon exposure to ROS, Nrf2 translocates to the nucleus allowing transcriptional activation of various antioxidant enzymes. DJ1 is a protein that is involved in the stabilization of Nrf2 and hence acts as a positive regulator of Nrf2-driven antioxidant protection. Here, we investigate the (sub)cellular localization of Nrf2 and DJ1 in various MS lesion stages and show that Nrf2 is strikingly upregulated in active MS lesions, in both the nucleus and the cytoplasm of infiltrating macrophages and to a lesser extent in reactive astrocytes. Simultaneously, DJ1 protein expression is predominantly increased in astrocytes in both active and chronic inactive MS lesions compared to control brain tissue and normal-appearing white matter. Together, our findings suggest that persistent Nrf2-mediated transcription occurs in active MS lesions, but that this endogenous response is insufficient to prevent ROS-induced cellular damage, which is abundant in inflammatory MS lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antioxidants / metabolism
  • Astrocytes / immunology
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Autopsy
  • Brain / immunology
  • Brain / metabolism*
  • Brain / pathology
  • Disease Progression
  • Encephalitis
  • Female
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / metabolism*
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / physiopathology
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / immunology
  • NF-E2-Related Factor 2 / metabolism*
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • Oxidative Stress
  • Protein Deglycase DJ-1
  • Protein Transport
  • Up-Regulation / immunology


  • Antioxidants
  • Intracellular Signaling Peptides and Proteins
  • NF-E2-Related Factor 2
  • Oncogene Proteins
  • PARK7 protein, human
  • Protein Deglycase DJ-1