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Prefoldin prevents aggregation of alpha-synuclein
| Title: | Prefoldin prevents aggregation of alpha-synuclein |
| Authors: | Takano, Mariko Browse this author | | Tashiro, Erika Browse this author | | Kitamura, Akira Browse this author | | Maita, Hiroshi Browse this author →KAKEN DB | | Iguchi-Ariga, Sanae M. M. Browse this author →KAKEN DB | | Kinjo, Masataka Browse this author →KAKEN DB | | Ariga, Hiroyoshi Browse this author →KAKEN DB |
| Keywords: | Prefoldin | | Chaperone | | alpha-Synuclein | | Protein aggregation | | Cell death |
| Issue Date: | 13-Jan-2014 |
| Publisher: | Elsevier science bv |
| Journal Title: | Brain research |
| Volume: | 1542 |
| Start Page: | 186 |
| End Page: | 194 |
| Publisher DOI: | 10.1016/j.brainres.2013.10.034 |
| PMID: | 24511594 |
| Abstract: | Protein aggregation is observed in various neurodegeneration diseases, including Parkinson's disease (PD). Alpha-synuclein, a causative gene product of familial PD, is a major component of large aggregates (inclusion bodies) in PD. Prefoldin, a molecular chaperone comprised of six subunits, PFD1 similar to 6, prevents misfolding of newly synthesized nascent polypeptides and also prevents aggregation of protein such as a' pathogenic form of Huntingtin, a causative gene product of Huntington disease. In this study, we first found that aggregation of TagRFP-tagged wild-type alpha-synuclein and its pathogenic mutants, but not that of GFP-tagged alpha-synuclein, occurred in transfected Neuro-2a cells. The fluorescence of GFP is weakened under the condition of pH 4.5-5.0, and TagRFP is a stable red fluorescence protein under an acidic condition. Aggregated TagRFP-wild-type alpha-synuclein and its pathogenic mutants in Neuro-2a cells were ubiquitinated and were colocalized with the prefoldin complex in the lysosome under this condition. Furthermore, knockdown of PFD2 and PFD5 disrupted prefoldin formation in alpha-synuclein-expressing cells, resulting in accumulation of aggregates of wild-type and pathogenic alpha-synuclein and in induction of cell death. The levels of aggregation and cell death in pathogenic alpha-synuclein-transfected cells tended to be higher than those in wild-type alpha-synuclein-transfected cells. These results suggest that prefoldin works as a protective factor in aggregated alpha-synucleininduced cell death. (C) 2013 Elsevier B.V. All rights reserved. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/54875 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 有賀 寛芳
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