Direct cellular delivery of human proteasomes to delay tau aggregation

Dong Hoon Han, Hee-Kyung Na, Won Hoon Choi, Jung Hoon Lee, Yun Kyung Kim, Cheolhee Won, Seung-Han Lee, Kwang Pyo Kim, Jeff Kuret, Dal-Hee Min () and Min Jae Lee ()
Additional contact information
Dong Hoon Han: College of Applied Sciences, Kyung Hee University
Hee-Kyung Na: Center for RNA Research, Institute for Basic Science, Seoul National University
Won Hoon Choi: College of Applied Sciences, Kyung Hee University
Jung Hoon Lee: College of Applied Sciences, Kyung Hee University
Yun Kyung Kim: Center for Neuro-Medicine, Korea Institute of Science & Technology (KIST)
Cheolhee Won: Center for RNA Research, Institute for Basic Science, Seoul National University
Seung-Han Lee: College of Applied Sciences, Kyung Hee University
Kwang Pyo Kim: College of Applied Sciences, Kyung Hee University
Jeff Kuret: Ohio State University
Dal-Hee Min: Center for RNA Research, Institute for Basic Science, Seoul National University
Min Jae Lee: College of Applied Sciences, Kyung Hee University

Nature Communications, 2014, vol. 5, issue 1, 1-8

Abstract: 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.

Date: 2014
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms6633 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6633

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms6633

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().