Hokkaido University Collection of Scholarly and Academic Papers >
Faculty of Pharmaceutical Sciences >
Peer-reviewed Journal Articles, etc >
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)
|
Submitter: 有賀 寛芳
|