DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation.

• Main Authors: Shoshana Shendelman, Alan Jonason, Cecile Martinat, Thomas Leete, Asa Abeliovich
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2004-11-01
• Series: PLoS Biology
• Online Access: https://doi.org/10.1371/journal.pbio.0020362

Parkinson's disease (PD) pathology is characterized by the degeneration of midbrain dopamine neurons (DNs) ultimately leading to a progressive movement disorder in patients. The etiology of DN loss in sporadic PD is unknown, although it is hypothesized that aberrant protein aggregation and cellular oxidative stress may promote DN degeneration. Homozygous mutations in DJ-1 were recently described in two families with autosomal recessive inherited PD (Bonifati et al. 2003). In a companion article (Martinat et al. 2004), we show that mutations in DJ-1 alter the cellular response to oxidative stress and proteasomal inhibition. Here we show that DJ-1 functions as a redox-sensitive molecular chaperone that is activated in an oxidative cytoplasmic environment. We further demonstrate that DJ-1 chaperone activity in vivo extends to alpha-synuclein, a protein implicated in PD pathogenesis.