DJ-1 can form β-sheet structured aggregates that co-localize with pathological amyloid deposits

Neurobiol Dis. 2020 Feb:134:104629. doi: 10.1016/j.nbd.2019.104629. Epub 2019 Nov 11.

Abstract

The loss of native function of the DJ-1 protein has been linked to the development of Parkinson's (PD) and other neurodegenerative diseases. Here we show that DJ-1 aggregates into β-sheet structured soluble and fibrillar aggregates in vitro under physiological conditions and that this process is promoted by the oxidation of its catalytic Cys106 residue. This aggregation resulted in the loss of its native biochemical glyoxalase function and in addition oxidized DJ-1 aggregates were observed to localize within Lewy bodies, neurofibrillary tangles and amyloid plaques in human PD and Alzheimer's (AD) patients' post-mortem brain tissue. These findings suggest that the aggregation of DJ-1 may be a critical player in the development of the pathology of PD and AD and demonstrate that loss of DJ-1 function can happen through DJ-1 aggregation. This could then contribute to AD and PD disease onset and progression.

Keywords: Aggregation; Alzheimer's; Amyloid; DJ-1; Parkinson's.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Brain / metabolism
  • Brain / pathology*
  • Humans
  • Lewy Bodies / chemistry
  • Lewy Bodies / metabolism
  • Lewy Bodies / pathology
  • Neurofibrillary Tangles / chemistry
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology*
  • Plaque, Amyloid / chemistry
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • Protein Aggregates
  • Protein Aggregation, Pathological / metabolism*
  • Protein Aggregation, Pathological / pathology
  • Protein Conformation, beta-Strand
  • Protein Deglycase DJ-1 / chemistry
  • Protein Deglycase DJ-1 / metabolism*

Substances

  • Protein Aggregates
  • PARK7 protein, human
  • Protein Deglycase DJ-1