title: DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation.
abstract: 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.
authors.affiliation: Department of Pathology, Center for Neurobiology and Behavior, and Taub Institute, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
authors.forename: Shoshana
authors.initials: S
authors.lastname: Shendelman
authors.forename: Alan
authors.initials: A
authors.lastname: Jonason
authors.forename: Cecile
authors.initials: C
authors.lastname: Martinat
authors.forename: Thomas
authors.initials: T
authors.lastname: Leete
authors.forename: Asa
authors.initials: A
authors.lastname: Abeliovich
mesh_terms: D000975:Antioxidants / Q000737:chemistry; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003545:Cysteine / Q000737:chemistry; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D004298:Dopamine / Q000378:metabolism; D005822:Genetic Vectors; D006367:HeLa Cells; D006720:Homozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D010300:Parkinson Disease / Q000378:metabolism; D000071617:Protein Deglycase DJ-1; D013053:Spectrophotometry; D051843:Synucleins / Q000737:chemistry; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D015513:Oncogene Proteins; D051843:Synucleins; D051844:alpha-Synuclein; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D003545:Cysteine; D010100:Oxygen; D004298:Dopamine