open access

https://hdl.handle.net/2115/54875

Prefoldin prevents aggregation of alpha-synuclein

英語

Cell death

2014-01-13

Elsevier science bv

Brain research

1542

186-194

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.

学術雑誌論文

Accepted Manuscript

0006-8993