Novel amplification mechanism of prions through disrupting sortilin-mediated trafficking
| العنوان: | Novel amplification mechanism of prions through disrupting sortilin-mediated trafficking |
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| المؤلفون: | Keiji Uchiyama, Suehiro Sakaguchi |
| المصدر: | Prion. 11:398-404 |
| بيانات النشر: | Informa UK Limited, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Gene isoform, Prions, animal diseases, Protein degradation, Inhibitory postsynaptic potential, Biochemistry, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, Lysosome, medicine, Animals, Humans, PrPC Proteins, Prion protein, Receptor, Chemistry, Mechanism (biology), Extra View, Cell Biology, nervous system diseases, Cell biology, Transport protein, Adaptor Proteins, Vesicular Transport, Protein Transport, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, nervous system, Lysosomes |
| الوصف: | Conformational conversion of the cellular prion protein, PrPC, into the abnormally folded isoform of prion protein, PrPSc, which leads to marked accumulation of PrPSc in brains, is a key pathogenic event in prion diseases, a group of fatal neurodegenerative disorders caused by prions. However, the exact mechanism of PrPSc accumulation in prion-infected neurons remains unknown. We recently reported a novel cellular mechanism to support PrPSc accumulation in prion-infected neurons, in which PrPSc itself promotes its accumulation by evading the cellular inhibitory mechanism, which is newly identified in our recent study. We showed that the VPS10P sorting receptor sortilin negatively regulates PrPSc accumulation in prion-infected neurons, by interacting with PrPC and PrPSc and trafficking them to lysosomes for degradation. However, PrPSc stimulated lysosomal degradation of sortilin, disrupting the sortilin-mediated degradation of PrPC and PrPSc and eventually evoking further accumulation of PrPSc in prion-infected neurons. These findings suggest a positive feedback amplification mechanism for PrPSc accumulation in prion-infected neurons. |
| تدمد: | 1933-690X 1933-6896 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9126bb2aa78b51aec314060753060efcTest https://doi.org/10.1080/19336896.2017.1391435Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9126bb2aa78b51aec314060753060efc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1933690X 19336896 |
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