Cathepsin D-deficient Drosophila recapitulate the key features of neuronal ceroid lipofuscinoses

Liisa Myllykangas, Jaana Tyynelä, Andrea Page-McCaw, Gerard M Rubin, Matti Haltia, Mel B Feany

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    Kuvaus

    Neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal storage disorders characterized pathologically by neuronal accumulation of autofluorescent storage material and neurodegeneration. An ovine NCL form is caused by a recessive point mutation in the cathepsin D gene, which encodes a lysosomal aspartyl protease. This mutation results in typical NCL pathology with neurodegeneration and characteristic neuronal storage material. We have generated a Drosophila NCL model by inactivating the conserved Drosophila cathepsin D homolog. We report here that cathepsin D mutant flies exhibit the key features of NCLs. They show progressive neuronal accumulation of autofluorescent storage inclusions, which are also positive for periodic acid Schiff and luxol fast blue stains. Ultrastructurally, the storage material is composed of membrane-bound granular electron-dense material, similar to the granular osmiophilic deposits found in the human infantile and ovine congenital NCL forms. In addition, cathepsin D mutant flies show modest age-dependent neurodegeneration. Our results suggest that the metabolic pathway leading to NCL pathology is highly conserved during evolution, and that cathepsin D mutant flies can be used to study the pathogenesis of NCLs. (c) 2005 Elsevier Inc. All rights reserved.
    Alkuperäiskielienglanti
    LehtiNeurobiology of Disease
    Vuosikerta19
    Numero1/2
    Sivut194-199
    Sivumäärä6
    ISSN0969-9961
    DOI - pysyväislinkit
    TilaJulkaistu - 2005
    OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

    Lainaa tätä

    Myllykangas, Liisa ; Tyynelä, Jaana ; Page-McCaw, Andrea ; Rubin, Gerard M ; Haltia, Matti ; Feany, Mel B. / Cathepsin D-deficient Drosophila recapitulate the key features of neuronal ceroid lipofuscinoses. Julkaisussa: Neurobiology of Disease. 2005 ; Vuosikerta 19, Nro 1/2. Sivut 194-199.
    @article{8513fc5b15794f7ba936057d0dac5bdd,
    title = "Cathepsin D-deficient Drosophila recapitulate the key features of neuronal ceroid lipofuscinoses",
    abstract = "Neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal storage disorders characterized pathologically by neuronal accumulation of autofluorescent storage material and neurodegeneration. An ovine NCL form is caused by a recessive point mutation in the cathepsin D gene, which encodes a lysosomal aspartyl protease. This mutation results in typical NCL pathology with neurodegeneration and characteristic neuronal storage material. We have generated a Drosophila NCL model by inactivating the conserved Drosophila cathepsin D homolog. We report here that cathepsin D mutant flies exhibit the key features of NCLs. They show progressive neuronal accumulation of autofluorescent storage inclusions, which are also positive for periodic acid Schiff and luxol fast blue stains. Ultrastructurally, the storage material is composed of membrane-bound granular electron-dense material, similar to the granular osmiophilic deposits found in the human infantile and ovine congenital NCL forms. In addition, cathepsin D mutant flies show modest age-dependent neurodegeneration. Our results suggest that the metabolic pathway leading to NCL pathology is highly conserved during evolution, and that cathepsin D mutant flies can be used to study the pathogenesis of NCLs. (c) 2005 Elsevier Inc. All rights reserved.",
    author = "Liisa Myllykangas and Jaana Tyynel{\"a} and Andrea Page-McCaw and Rubin, {Gerard M} and Matti Haltia and Feany, {Mel B}",
    year = "2005",
    doi = "10.1016/j.nbd.2004.12.019",
    language = "English",
    volume = "19",
    pages = "194--199",
    journal = "Neurobiology of Disease",
    issn = "0969-9961",
    publisher = "ACADEMIC PRESS INC ELSEVIER SCIENCE",
    number = "1/2",

    }

    Cathepsin D-deficient Drosophila recapitulate the key features of neuronal ceroid lipofuscinoses. / Myllykangas, Liisa; Tyynelä, Jaana; Page-McCaw, Andrea; Rubin, Gerard M; Haltia, Matti; Feany, Mel B.

    julkaisussa: Neurobiology of Disease, Vuosikerta 19, Nro 1/2, 2005, s. 194-199.

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    TY - JOUR

    T1 - Cathepsin D-deficient Drosophila recapitulate the key features of neuronal ceroid lipofuscinoses

    AU - Myllykangas, Liisa

    AU - Tyynelä, Jaana

    AU - Page-McCaw, Andrea

    AU - Rubin, Gerard M

    AU - Haltia, Matti

    AU - Feany, Mel B

    PY - 2005

    Y1 - 2005

    N2 - Neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal storage disorders characterized pathologically by neuronal accumulation of autofluorescent storage material and neurodegeneration. An ovine NCL form is caused by a recessive point mutation in the cathepsin D gene, which encodes a lysosomal aspartyl protease. This mutation results in typical NCL pathology with neurodegeneration and characteristic neuronal storage material. We have generated a Drosophila NCL model by inactivating the conserved Drosophila cathepsin D homolog. We report here that cathepsin D mutant flies exhibit the key features of NCLs. They show progressive neuronal accumulation of autofluorescent storage inclusions, which are also positive for periodic acid Schiff and luxol fast blue stains. Ultrastructurally, the storage material is composed of membrane-bound granular electron-dense material, similar to the granular osmiophilic deposits found in the human infantile and ovine congenital NCL forms. In addition, cathepsin D mutant flies show modest age-dependent neurodegeneration. Our results suggest that the metabolic pathway leading to NCL pathology is highly conserved during evolution, and that cathepsin D mutant flies can be used to study the pathogenesis of NCLs. (c) 2005 Elsevier Inc. All rights reserved.

    AB - Neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal storage disorders characterized pathologically by neuronal accumulation of autofluorescent storage material and neurodegeneration. An ovine NCL form is caused by a recessive point mutation in the cathepsin D gene, which encodes a lysosomal aspartyl protease. This mutation results in typical NCL pathology with neurodegeneration and characteristic neuronal storage material. We have generated a Drosophila NCL model by inactivating the conserved Drosophila cathepsin D homolog. We report here that cathepsin D mutant flies exhibit the key features of NCLs. They show progressive neuronal accumulation of autofluorescent storage inclusions, which are also positive for periodic acid Schiff and luxol fast blue stains. Ultrastructurally, the storage material is composed of membrane-bound granular electron-dense material, similar to the granular osmiophilic deposits found in the human infantile and ovine congenital NCL forms. In addition, cathepsin D mutant flies show modest age-dependent neurodegeneration. Our results suggest that the metabolic pathway leading to NCL pathology is highly conserved during evolution, and that cathepsin D mutant flies can be used to study the pathogenesis of NCLs. (c) 2005 Elsevier Inc. All rights reserved.

    U2 - 10.1016/j.nbd.2004.12.019

    DO - 10.1016/j.nbd.2004.12.019

    M3 - Article

    VL - 19

    SP - 194

    EP - 199

    JO - Neurobiology of Disease

    JF - Neurobiology of Disease

    SN - 0969-9961

    IS - 1/2

    ER -