A role for a novel protein, nucleolin, in Parkinson's disease.
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.
Caudle
W Michael
WM
Department of Pathology, University of Washington School of Medicine, Seattle, WA 98104, United States.
Kitsou
Efstathia
E
Li
Jane
J
Bradner
Joshua
J
Zhang
Jing
J
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
D042967:Electron Transport Complex I; D009498:Neurotoxins; D010750:Phosphoproteins; D046988:Proteasome Endopeptidase Complex; D016601:RNA-Binding Proteins; D012402:Rotenone; D000097796:Nucleolin