title: DJ-1 is present in a large molecular complex in human brain tissue and interacts with alpha-synuclein.
abstract: DJ-1 is a ubiquitously expressed protein involved in various cellular processes including cell proliferation, RNA-binding, and oxidative stress. Mutations that result in loss of DJ-1 function lead to early onset parkinsonism in humans, and DJ-1 protein is present in pathological lesions of several tauopathies and synucleinopathies. In order to further investigate the role of DJ-1 in human neurodegenerative disease, we have generated novel polyclonal and monoclonal antibodies to human DJ-1 protein. We have characterized these antibodies and confirmed the pathological co-localization of DJ-1 with other neurodegenerative disease-associated proteins, as well as the decrease in DJ-1 solubility in disease tissue. In addition, we report the presence of DJ-1 in a large molecular complex (> 2000 kDa), and provide evidence for an interaction between endogenous DJ-1 and alpha-synuclein in normal and diseased tissue. These findings provide new avenues towards the study of DJ-1 function and how loss of its activity may lead to parkinsonism. Furthermore, our results provide further evidence for the interplay between neurodegenerative disease-associated proteins.
authors.affiliation: Department of Biology and Laboratory of Medicine of University of Pennsylvania, Philadelphia 19104-6084, USA.
authors.forename: Marc C
authors.initials: MC
authors.lastname: Meulener
authors.forename: Charles L
authors.initials: CL
authors.lastname: Graves
authors.forename: Deepak M
authors.initials: DM
authors.lastname: Sampathu
authors.forename: Cecilia E
authors.initials: CE
authors.lastname: Armstrong-Gold
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Bonini
authors.forename: Benoit I
authors.initials: BI
authors.lastname: Giasson
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D004330:Drosophila; D006801:Humans; D002479:Inclusion Bodies / Q000276:immunology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009410:Nerve Degeneration / Q000378:metabolism* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D015513:Oncogene Proteins / Q000276:immunology / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism / Q000503:physiopathology; D000071617:Protein Deglycase DJ-1; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins / Q000378:metabolism
chemical_list: D000906:Antibodies; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; C497604:SNCA protein, human; C497605:Snca protein, mouse; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1