Strain-Dependent Effect of Macroautophagy on Abnormally Folded Prion Protein Degradation in Infected Neuronal Cells.
Prion diseases are neurodegenerative disorders caused by the accumulation of abnormal prion protein (PrPSc) in the central nervous system. With the aim of elucidating the mechanism underlying the accumulation and degradation of PrPSc, we investigated the role of autophagy in its degradation, using c...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4569470?pdf=render |
| _version_ | 1819018711071195136 |
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| author | Daisuke Ishibashi Takujiro Homma Takehiro Nakagaki Takayuki Fuse Kazunori Sano Hanae Takatsuki Ryuichiro Atarashi Noriyuki Nishida |
| author_facet | Daisuke Ishibashi Takujiro Homma Takehiro Nakagaki Takayuki Fuse Kazunori Sano Hanae Takatsuki Ryuichiro Atarashi Noriyuki Nishida |
| author_sort | Daisuke Ishibashi |
| collection | DOAJ |
| description | Prion diseases are neurodegenerative disorders caused by the accumulation of abnormal prion protein (PrPSc) in the central nervous system. With the aim of elucidating the mechanism underlying the accumulation and degradation of PrPSc, we investigated the role of autophagy in its degradation, using cultured cells stably infected with distinct prion strains. The effects of pharmacological compounds that inhibit or stimulate the cellular signal transduction pathways that mediate autophagy during PrPSc degradation were evaluated. The accumulation of PrPSc in cells persistently infected with the prion strain Fukuoka-1 (FK), derived from a patient with Gerstmann-Sträussler-Scheinker syndrome, was significantly increased in cultures treated with the macroautophagy inhibitor 3-methyladenine (3MA) but substantially reduced in those treated with the macroautophagy inducer rapamycin. The decrease in FK-derived PrPSc levels was mediated, at least in part, by the phosphatidylinositol 3-kinase/MEK signalling pathway. By contrast, neither rapamycin nor 3MA had any apparently effect on PrPSc from either the 22L or the Chandler strain, indicating that the degradation of PrPSc in host cells might be strain-dependent. |
| first_indexed | 2024-12-21T03:23:45Z |
| format | Article |
| id | doaj.art-188e0eefd34d49a2b9c93cc0e807a221 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T03:23:45Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-188e0eefd34d49a2b9c93cc0e807a2212022-12-21T19:17:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013795810.1371/journal.pone.0137958Strain-Dependent Effect of Macroautophagy on Abnormally Folded Prion Protein Degradation in Infected Neuronal Cells.Daisuke IshibashiTakujiro HommaTakehiro NakagakiTakayuki FuseKazunori SanoHanae TakatsukiRyuichiro AtarashiNoriyuki NishidaPrion diseases are neurodegenerative disorders caused by the accumulation of abnormal prion protein (PrPSc) in the central nervous system. With the aim of elucidating the mechanism underlying the accumulation and degradation of PrPSc, we investigated the role of autophagy in its degradation, using cultured cells stably infected with distinct prion strains. The effects of pharmacological compounds that inhibit or stimulate the cellular signal transduction pathways that mediate autophagy during PrPSc degradation were evaluated. The accumulation of PrPSc in cells persistently infected with the prion strain Fukuoka-1 (FK), derived from a patient with Gerstmann-Sträussler-Scheinker syndrome, was significantly increased in cultures treated with the macroautophagy inhibitor 3-methyladenine (3MA) but substantially reduced in those treated with the macroautophagy inducer rapamycin. The decrease in FK-derived PrPSc levels was mediated, at least in part, by the phosphatidylinositol 3-kinase/MEK signalling pathway. By contrast, neither rapamycin nor 3MA had any apparently effect on PrPSc from either the 22L or the Chandler strain, indicating that the degradation of PrPSc in host cells might be strain-dependent.http://europepmc.org/articles/PMC4569470?pdf=render |
| spellingShingle | Daisuke Ishibashi Takujiro Homma Takehiro Nakagaki Takayuki Fuse Kazunori Sano Hanae Takatsuki Ryuichiro Atarashi Noriyuki Nishida Strain-Dependent Effect of Macroautophagy on Abnormally Folded Prion Protein Degradation in Infected Neuronal Cells. PLoS ONE |
| title | Strain-Dependent Effect of Macroautophagy on Abnormally Folded Prion Protein Degradation in Infected Neuronal Cells. |
| title_full | Strain-Dependent Effect of Macroautophagy on Abnormally Folded Prion Protein Degradation in Infected Neuronal Cells. |
| title_fullStr | Strain-Dependent Effect of Macroautophagy on Abnormally Folded Prion Protein Degradation in Infected Neuronal Cells. |
| title_full_unstemmed | Strain-Dependent Effect of Macroautophagy on Abnormally Folded Prion Protein Degradation in Infected Neuronal Cells. |
| title_short | Strain-Dependent Effect of Macroautophagy on Abnormally Folded Prion Protein Degradation in Infected Neuronal Cells. |
| title_sort | strain dependent effect of macroautophagy on abnormally folded prion protein degradation in infected neuronal cells |
| url | http://europepmc.org/articles/PMC4569470?pdf=render |
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