Genetic modifiers of degeneration in the cathepsin D deficient Drosophila model for neuronal ceroid lipofuscinosis
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: progressiv...
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| Format: | Article |
| Language: | English |
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Elsevier
2009-12-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996109002423 |
| _version_ | 1818673284265279488 |
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| author | Mervi Kuronen Minnamari Talvitie Anna-Elina Lehesjoki Liisa Myllykangas |
| author_facet | Mervi Kuronen Minnamari Talvitie Anna-Elina Lehesjoki Liisa Myllykangas |
| author_sort | Mervi Kuronen |
| collection | DOAJ |
| description | 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. |
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| format | Article |
| id | doaj.art-7505e1c4407c4255b67fe8f3f83e0333 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T07:53:21Z |
| publishDate | 2009-12-01 |
| publisher | Elsevier |
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| series | Neurobiology of Disease |
| spelling | doaj.art-7505e1c4407c4255b67fe8f3f83e03332022-12-21T21:57:47ZengElsevierNeurobiology of Disease1095-953X2009-12-01363488493Genetic modifiers of degeneration in the cathepsin D deficient Drosophila model for neuronal ceroid lipofuscinosisMervi Kuronen0Minnamari Talvitie1Anna-Elina Lehesjoki2Liisa Myllykangas3Folkhälsan Institute of Genetics, Biomedicum Helsinki, Helsinki, Finland; Department of Medical Genetics and Neuroscience Center, University of Helsinki, Helsinki, FinlandFolkhälsan Institute of Genetics, Biomedicum Helsinki, Helsinki, FinlandFolkhälsan Institute of Genetics, Biomedicum Helsinki, Helsinki, Finland; Department of Medical Genetics and Neuroscience Center, University of Helsinki, Helsinki, FinlandFolkhälsan Institute of Genetics, Biomedicum Helsinki, Helsinki, Finland; Department of Pathology, University of Helsinki and HUSLAB, Helsinki, Finland; Corresponding author. Folkhälsan Institute of Genetics, Biomedicum Helsinki, POB 63, 00014 University of Helsinki, Finland. Fax: +358 9 19125073.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.http://www.sciencedirect.com/science/article/pii/S0969996109002423Cathepsin DDrosophilaNeurodegenerationGenetic modifier |
| spellingShingle | Mervi Kuronen Minnamari Talvitie Anna-Elina Lehesjoki Liisa Myllykangas Genetic modifiers of degeneration in the cathepsin D deficient Drosophila model for neuronal ceroid lipofuscinosis Neurobiology of Disease Cathepsin D Drosophila Neurodegeneration Genetic modifier |
| title | Genetic modifiers of degeneration in the cathepsin D deficient Drosophila model for neuronal ceroid lipofuscinosis |
| title_full | Genetic modifiers of degeneration in the cathepsin D deficient Drosophila model for neuronal ceroid lipofuscinosis |
| title_fullStr | Genetic modifiers of degeneration in the cathepsin D deficient Drosophila model for neuronal ceroid lipofuscinosis |
| title_full_unstemmed | Genetic modifiers of degeneration in the cathepsin D deficient Drosophila model for neuronal ceroid lipofuscinosis |
| title_short | Genetic modifiers of degeneration in the cathepsin D deficient Drosophila model for neuronal ceroid lipofuscinosis |
| title_sort | genetic modifiers of degeneration in the cathepsin d deficient drosophila model for neuronal ceroid lipofuscinosis |
| topic | Cathepsin D Drosophila Neurodegeneration Genetic modifier |
| url | http://www.sciencedirect.com/science/article/pii/S0969996109002423 |
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