2016 Fiscal Year Final Research Report
Pathophysiology of lysosomal storage disease and lysophagy
| Project/Area Number |
15H05673
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Kawasaki Medical School (2016)
Osaka University (2015) |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | リソソーム蓄積病 / オートファジー / EPG5 / VPS33A |
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| Outline of Final Research Achievements |
(i) Intracellular accumulation of cholesterol that is often observed in lysosomal storage diseases affects lysosomal membrane permeability. We identified a candidate molecule which works for ubiquitin ligase in the autophagic process following lysosomal membrane rupture. (ii) We analyzed skin fibroblasts from patients of Vici syndrome, which is caused by mutations of EPG5 gene, and elucidated that EPG5 functions for the fusion step between autophagosome and lysosome. (iii) Using whole exome sequencing, we established a novel syndrome which is caused by mutations of VPS33A gene (Mucopolysaccharidosis Plus Syndrome, OMIM #617303), and reported a part of pathophysiology of this new disease. Altogether we proved that not only undegraded substrates of lysosomal enzymes but also membrane lipid contents and intracellular vesicular trafficking are complicatedly implicated in the pathophysiology of lysosomal storage diseases.
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| Free Research Field |
小児科学
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