Genetic modifiers of degeneration in the cathepsin D deficient Drosophila model for neuronal ceroid lipofuscinosis

Mervi Kuronen, Minnamari Talvitie, Anna-Elina Lehesjoki, Liisa Myllykangas

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    Kuvaus

    Neuronal ceroid lipofuscinoses (NCLs) are pediatric, neurodegenerative, lysosomal storage disorders. Mutations in cathepsin D result in the most severe, congenital form of NCLs. We have previously generated a cathepsin D deficient Drosophila model, which exhibits the key features of NCLs: progressive intracellular accumulation of autofluorescent storage material and modest neurodegeneration in the brain areas related to visual functions. Here we extend the phenotypic characterization of cathepsin D deficient Drosophila and report that modest degenerative changes are also present in their retinae. Furthermore, by utilizing this phenotype, we examined the possible effect of 17 candidate modifiers, selected based on the results from other cathepsin D deficiency models. We found enhancers of this phenotype that support the involvement of endocytosis-, lipid metabolism- and oxidation-related factors in the cathepsin D deficiency induced degeneration. Our results warrant further investigation of these mechanisms in the pathogenesis of cathepsin D deficiency. (C) 2009 Elsevier Inc. All rights reserved.
    Alkuperäiskielienglanti
    LehtiNeurobiology of Disease
    Vuosikerta36
    Numero3
    Sivut488-493
    Sivumäärä6
    ISSN0969-9961
    DOI - pysyväislinkit
    TilaJulkaistu - 2009
    OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

    Tieteenalat

    • 311 Peruslääketieteet
    • 118 Biotieteet
    • 515 Psykologia

    Lainaa tätä

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    title = "Genetic modifiers of degeneration in the cathepsin D deficient Drosophila model for neuronal ceroid lipofuscinosis",
    abstract = "Neuronal ceroid lipofuscinoses (NCLs) are pediatric, neurodegenerative, lysosomal storage disorders. Mutations in cathepsin D result in the most severe, congenital form of NCLs. We have previously generated a cathepsin D deficient Drosophila model, which exhibits the key features of NCLs: progressive intracellular accumulation of autofluorescent storage material and modest neurodegeneration in the brain areas related to visual functions. Here we extend the phenotypic characterization of cathepsin D deficient Drosophila and report that modest degenerative changes are also present in their retinae. Furthermore, by utilizing this phenotype, we examined the possible effect of 17 candidate modifiers, selected based on the results from other cathepsin D deficiency models. We found enhancers of this phenotype that support the involvement of endocytosis-, lipid metabolism- and oxidation-related factors in the cathepsin D deficiency induced degeneration. Our results warrant further investigation of these mechanisms in the pathogenesis of cathepsin D deficiency. (C) 2009 Elsevier Inc. All rights reserved.",
    keywords = "311 Basic medicine, 118 Biological sciences, 515 Psychology",
    author = "Mervi Kuronen and Minnamari Talvitie and Anna-Elina Lehesjoki and Liisa Myllykangas",
    year = "2009",
    doi = "10.1016/j.nbd.2009.09.001",
    language = "English",
    volume = "36",
    pages = "488--493",
    journal = "Neurobiology of Disease",
    issn = "0969-9961",
    publisher = "ACADEMIC PRESS INC ELSEVIER SCIENCE",
    number = "3",

    }

    Genetic modifiers of degeneration in the cathepsin D deficient Drosophila model for neuronal ceroid lipofuscinosis. / Kuronen, Mervi; Talvitie, Minnamari; Lehesjoki, Anna-Elina; Myllykangas, Liisa.

    julkaisussa: Neurobiology of Disease, Vuosikerta 36, Nro 3, 2009, s. 488-493.

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    TY - JOUR

    T1 - Genetic modifiers of degeneration in the cathepsin D deficient Drosophila model for neuronal ceroid lipofuscinosis

    AU - Kuronen, Mervi

    AU - Talvitie, Minnamari

    AU - Lehesjoki, Anna-Elina

    AU - Myllykangas, Liisa

    PY - 2009

    Y1 - 2009

    N2 - Neuronal ceroid lipofuscinoses (NCLs) are pediatric, neurodegenerative, lysosomal storage disorders. Mutations in cathepsin D result in the most severe, congenital form of NCLs. We have previously generated a cathepsin D deficient Drosophila model, which exhibits the key features of NCLs: progressive intracellular accumulation of autofluorescent storage material and modest neurodegeneration in the brain areas related to visual functions. Here we extend the phenotypic characterization of cathepsin D deficient Drosophila and report that modest degenerative changes are also present in their retinae. Furthermore, by utilizing this phenotype, we examined the possible effect of 17 candidate modifiers, selected based on the results from other cathepsin D deficiency models. We found enhancers of this phenotype that support the involvement of endocytosis-, lipid metabolism- and oxidation-related factors in the cathepsin D deficiency induced degeneration. Our results warrant further investigation of these mechanisms in the pathogenesis of cathepsin D deficiency. (C) 2009 Elsevier Inc. All rights reserved.

    AB - Neuronal ceroid lipofuscinoses (NCLs) are pediatric, neurodegenerative, lysosomal storage disorders. Mutations in cathepsin D result in the most severe, congenital form of NCLs. We have previously generated a cathepsin D deficient Drosophila model, which exhibits the key features of NCLs: progressive intracellular accumulation of autofluorescent storage material and modest neurodegeneration in the brain areas related to visual functions. Here we extend the phenotypic characterization of cathepsin D deficient Drosophila and report that modest degenerative changes are also present in their retinae. Furthermore, by utilizing this phenotype, we examined the possible effect of 17 candidate modifiers, selected based on the results from other cathepsin D deficiency models. We found enhancers of this phenotype that support the involvement of endocytosis-, lipid metabolism- and oxidation-related factors in the cathepsin D deficiency induced degeneration. Our results warrant further investigation of these mechanisms in the pathogenesis of cathepsin D deficiency. (C) 2009 Elsevier Inc. All rights reserved.

    KW - 311 Basic medicine

    KW - 118 Biological sciences

    KW - 515 Psychology

    U2 - 10.1016/j.nbd.2009.09.001

    DO - 10.1016/j.nbd.2009.09.001

    M3 - Article

    VL - 36

    SP - 488

    EP - 493

    JO - Neurobiology of Disease

    JF - Neurobiology of Disease

    SN - 0969-9961

    IS - 3

    ER -