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  1. Article ; Online: Mitochondrial translocation of alpha-synuclein is promoted by intracellular acidification.

    Cole, Nelson B / Dieuliis, Diane / Leo, Paul / Mitchell, Drake C / Nussbaum, Robert L

    Experimental cell research

    2008  Volume 314, Issue 10, Page(s) 2076–2089

    Abstract: Mitochondrial dysfunction plays a central role in the selective vulnerability of dopaminergic neurons in Parkinson's disease (PD) and is influenced by both environmental and genetic factors. Expression of the PD protein alpha-synuclein or its familial ... ...

    Abstract Mitochondrial dysfunction plays a central role in the selective vulnerability of dopaminergic neurons in Parkinson's disease (PD) and is influenced by both environmental and genetic factors. Expression of the PD protein alpha-synuclein or its familial mutants often sensitizes neurons to oxidative stress and to damage by mitochondrial toxins. This effect is thought to be indirect, since little evidence physically linking alpha-synuclein to mitochondria has been reported. Here, we show that the distribution of alpha-synuclein within neuronal and non-neuronal cells is dependent on intracellular pH. Cytosolic acidification induces translocation of alpha-synuclein from the cytosol onto the surface of mitochondria. Translocation occurs rapidly under artificially-induced low pH conditions and as a result of pH changes during oxidative or metabolic stress. Binding is likely facilitated by low pH-induced exposure of the mitochondria-specific lipid cardiolipin. These results imply a direct role for alpha-synuclein in mitochondrial physiology, especially under pathological conditions, and in principle, link alpha-synuclein to other PD genes in regulating mitochondrial homeostasis.
    MeSH term(s) Antimetabolites/metabolism ; Carbonyl Cyanide m-Chlorophenyl Hydrazone/metabolism ; Cell Line ; Deoxyglucose/metabolism ; Enzyme Inhibitors/metabolism ; Humans ; Hydrogen Peroxide/metabolism ; Hydrogen-Ion Concentration ; Mitochondria/metabolism ; Mitochondria/ultrastructure ; Mitochondrial Membranes/metabolism ; Mitochondrial Membranes/ultrastructure ; Oxidants/metabolism ; Oxidative Stress ; Parkinson Disease/genetics ; Parkinson Disease/metabolism ; Protein Binding ; Protein Transport ; Sodium Azide/metabolism ; Uncoupling Agents/metabolism ; alpha-Synuclein/genetics ; alpha-Synuclein/metabolism
    Chemical Substances Antimetabolites ; Enzyme Inhibitors ; Oxidants ; Uncoupling Agents ; alpha-Synuclein ; Carbonyl Cyanide m-Chlorophenyl Hydrazone (555-60-2) ; Sodium Azide (968JJ8C9DV) ; Deoxyglucose (9G2MP84A8W) ; Hydrogen Peroxide (BBX060AN9V)
    Language English
    Publishing date 2008-03-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 1493-x
    ISSN 1090-2422 ; 0014-4827
    ISSN (online) 1090-2422
    ISSN 0014-4827
    DOI 10.1016/j.yexcr.2008.03.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 563: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: A longitudinal program for biomarker development in Parkinson's disease: a feasibility study.

    Ravina, Bernard / Tanner, Caroline / Dieuliis, Diane / Eberly, Shirley / Flagg, Emily / Galpern, Wendy R / Fahn, Stanley / Goetz, Christopher G / Grate, Stephen / Kurlan, Roger / Lang, Anthony E / Marek, Kenneth / Kieburtz, Karl / Oakes, David / Elliott, Robin / Shoulson, Ira

    Movement disorders : official journal of the Movement Disorder Society

    2009  Volume 24, Issue 14, Page(s) 2081–2090

    Abstract: Long-term follow up is necessary to understand the natural history of treated Parkinson's disease (PD). The Longitudinal and Biomarker Study in PD (LABS-PD) is an observational study designed to prospectively measure the evolution of motor and non-motor ... ...

    Abstract Long-term follow up is necessary to understand the natural history of treated Parkinson's disease (PD). The Longitudinal and Biomarker Study in PD (LABS-PD) is an observational study designed to prospectively measure the evolution of motor and non-motor features of PD and sample promising biomarkers from early to late stage illness. LABS-PD is organized on the premise that cohorts from completed clinical trials can be re-recruited for long-term follow up. LABS-PD will eventually contain multiple cohorts, but to test the feasibility of the strategy, we examined enrollment and biomarker sampling in the initial cohorts. The first PD cohort (PostCEPT) comes from the de novo clinical trial of a mixed lineage kinase inhibitor (PRECEPT). We assessed the recruitment from PRECEPT to PostCEPT, the ability to link data from the two studies, and sample collection for a variety of biomarkers. A total of 537 of 709 eligible PRECEPT subjects (76%) enrolled in PostCEPT; 509 (95%) had repeat dopamine transporter imaging. PRECEPT clinical and imaging data were successfully linked to PostCEPT, to provide 3 to 4 year follow-up. A biomarker sub-study enrolled over 100 PD cases from PostCEPT and 100 controls to measure olfaction and blood markers of gene expression, alpha-synuclein, and proteomic profiles. We were also successful in linking clinical and biomarker data to DNA samples that have been collected in the publicly accessible Coriell repository. The PostCEPT cohort and associated studies strongly support the feasibility of the LABS-PD approach of retaining and repurposing clinical trial cohorts to collect longitudinal clinical and biomarker data.
    MeSH term(s) Aged ; Biomarkers ; Clinical Trials as Topic ; Cohort Studies ; DNA/genetics ; Data Interpretation, Statistical ; Feasibility Studies ; Female ; Follow-Up Studies ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Movement/physiology ; Parkinson Disease/diagnosis ; Patient Selection
    Chemical Substances Biomarkers ; DNA (9007-49-2)
    Language English
    Publishing date 2009-10-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 607633-6
    ISSN 1531-8257 ; 0885-3185
    ISSN (online) 1531-8257
    ISSN 0885-3185
    DOI 10.1002/mds.22690
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2555: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 238: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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