title: A role for a novel protein, nucleolin, in Parkinson's disease.
abstract: Although much has been learned in the last few decades concerning the molecular mechanisms and pathways associated with the development of familial as well as sporadic Parkinson disease (PD), the precise mechanisms and specific proteins responsible for mediating these effects remain to be elucidated. Thus, the identification and biological evaluation of novel proteins involved in these pathways is critical to providing a more comprehensive understanding of PD pathogenesis. Previously, in a cellular model of PD, we identified nucleolin as a protein interacting with alpha-synuclein and DJ-1, two critical proteins involved in PD pathogenesis. In our current study, we found the expression levels of nucleolin were dramatically reduced in the substantia nigra pars compacta of human PD subjects, compared with controls. Furthermore, manipulation of nucleolin in an in vitro model of PD resulted in significant alterations in the generation of oxidative stress as well as proteasomal inhibition following rotenone exposure. Interestingly, nucleolin expression did not influence mitochondrial complex I activity, suggesting a selective specificity for oxidative stress and proteasomal pathways.
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA 98104, United States.
authors.forename: W Michael
authors.initials: WM
authors.lastname: Caudle
authors.forename: Efstathia
authors.initials: E
authors.lastname: Kitsou
authors.forename: Jane
authors.initials: J
authors.lastname: Li
authors.forename: Joshua
authors.initials: J
authors.lastname: Bradner
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009498:Neurotoxins / Q000633:toxicity; D018384:Oxidative Stress / Q000502:physiology; D010300:Parkinson Disease / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012402:Rotenone / Q000633:toxicity; D015398:Signal Transduction; D013378:Substantia Nigra / Q000378:metabolism*; D000097796:Nucleolin
chemical_list: D042967:Electron Transport Complex I; D009498:Neurotoxins; D010750:Phosphoproteins; D046988:Proteasome Endopeptidase Complex; D016601:RNA-Binding Proteins; D012402:Rotenone; D000097796:Nucleolin