HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Faculty of Pharmaceutical Sciences >
Peer-reviewed Journal Articles, etc >

Prefoldin prevents aggregation of alpha-synuclein

Files in This Item:
WoS_64420_Ariga.pdf5.63 MBPDFView/Open
Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/54875

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

Export metadata:

OAI-PMH ( junii2 , jpcoar )

MathJax is now OFF:


 

 - Hokkaido University