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  • Differential SUMO-1 distribution in Parkinson’s Disease patient neurosphere-derived cells in response to proteolytic stress

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    80133_1.pdf (275.7Kb)
    Author(s)
    Wong, Matthew Jun Lin
    Cook, Anthony L
    Mackay-Sim, Alan
    Pountney, Dean Louis
    Griffith University Author(s)
    Mackay-Sim, Alan
    Pountney, Dean L.
    Wong, Mathew B.
    Year published
    2012
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    Abstract
    We compared human olfactory mucosa-neurosphere (hONS) derived cell lines from patients with idiopathic PD to those from healthy control donors to investigate differences in the response to proteolytic stress. Immunotyping of these cells has revealed a phenotype that shares features with neural stem cells and bone marrow mesenchymal stromal/stem cells. We used hONS cell cultures to reveal differences in the histological distribution of the small ubiquitin-like modifier (SUMO--synuclein between Patients and Controls. Using immunofluorescence, we found specific labelling of a high-proportion of lysosomes with SUMO-1 in both PD ...
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    We compared human olfactory mucosa-neurosphere (hONS) derived cell lines from patients with idiopathic PD to those from healthy control donors to investigate differences in the response to proteolytic stress. Immunotyping of these cells has revealed a phenotype that shares features with neural stem cells and bone marrow mesenchymal stromal/stem cells. We used hONS cell cultures to reveal differences in the histological distribution of the small ubiquitin-like modifier (SUMO--synuclein between Patients and Controls. Using immunofluorescence, we found specific labelling of a high-proportion of lysosomes with SUMO-1 in both PD (25.5%±6.5; n=5) and Control (17.3%±4.8; n=5) cell lines after 24hrs treatment wi-treated (15.3%±4.2 and 7.4%±2.7, respectively). This is consistent with the lysosomal SUMO-1 labelling found recently in post-mortem human diseased tissue. There was a significantly (p = 0.025) greater proportion of SUMO-1-positive lysosomes in treated PD compared to treated Control cells, but a greater proportionate increase in SUMO-1-positive lysosomes at 24 hrs post-treatment in Control (2.3-fold) compared to PD cells (1.7--synuclein aggregates were observed more frequently in PD than Control cells in response to proteasome inhibition (p = 0.03), but were not significantly different in untreated cells. Total lysosome counts were increased in MG132-treated cells, but were equal in both PD and Control cells. This implicates both SUMO-1 and the regulation of the lysosome-autophagy pathway as being different on a disease basis in hONS cells.
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    Conference Title
    Proteostasis & Disease Symposium
    Publisher URI
    http://proteostasis2012.com.au/2012/
    http://proteostasis2012.com.au/2012/wp-content/uploads/2012/11/Dean-L.-Pountney.pdf
    Copyright Statement
    © 2012 Leishman Associates. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the conference's website for access to the definitive, published version.
    Subject
    Neurology and Neuromuscular Diseases
    Publication URI
    http://hdl.handle.net/10072/53543
    Collection
    • Conference outputs

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