Direct cellular delivery of human proteasomes to delay tau aggregation

Cited 35 time in webofscience Cited 0 time in scopus
486 Viewed 188 Downloaded
Title
Direct cellular delivery of human proteasomes to delay tau aggregation
Author(s)
Han, DH; Hee-Kyung Na; Choi, WH; Lee, JH; Kim, YK; Cheolhee Won; Lee, SH; Kim, KP; Kuret, J; Dal-Hee Min; Lee, MJ
Publication Date
2014-12
Journal
NATURE COMMUNICATIONS, v.5, no., pp.5633 -
Publisher
NATURE PUBLISHING GROUP
Abstract
The 26S proteasome is the primary machinery that degrades ubiquitin (Ub)-conjugated proteins, including many proteotoxic proteins implicated in neurodegeneraton. It has been suggested that the elevation of proteasomal activity is tolerable to cells and may be beneficial to prevent the accumulation of protein aggregates. Here we show that purified proteasomes can be directly transported into cells through mesoporous silica nanoparticle-mediated endocytosis. Proteasomes that are loaded onto nanoparticles through non-covalent interactions between polyhistidine tags and nickel ions fully retain their proteolytic activity. Cells treated with exogenous proteasomes are more efficient in degrading overexpressed human tau than endogenous proteasomal substrates, resulting in decreased levels of tau aggregates. Moreover, exogenous proteasome delivery significantly promotes cell survival against proteotoxic stress caused by tau and reactive oxygen species. These data demonstrate that increasing cellular proteasome activity through the direct delivery of purified proteasomes may be an effective strategy for reducing cellular levels of proteotoxic proteins.
URI
http://pr.ibs.re.kr/handle/8788114/838
DOI
10.1038/ncomms6633
ISSN
2041-1723
Appears in Collections:
Center for RNA Research(RNA 연구단) > Journal Papers (저널논문)
Files in This Item:
ncomms6633 (1).pdfDownload

qrcode

  • facebook

    twitter

  • Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse