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Acta Biochim Biophys Sin (Shanghai). 2014 Jul;46(7):531-9. doi: 10.1093/abbs/gmu031. Epub 2014 May 14.

Regulation of proteasomes in prion disease.

Author information

1
State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
2
State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China yanglf@cau.edu.cn.

Abstract

The hallmark of prion disease is the accumulation of misfolded protein PrP(Sc), which is toxic to neuronal cells. The proteasome system is responsible for the rapid, precise, and timely degradation of proteins and plays an important role in cellular protein quality control. Increasing evidence indicates impaired activity of proteasomes in prion diseases. Accumulated PrP(Sc) can directly or indirectly affect proteasome activity. Misfolded protein may influence the assembly and activity of 19S regulatory particle, or post-translational modification of 20S proteasome, which may adversely affect the protein degradation activity of proteasomes. In this review, we summarized the recent findings concerning the possible regulation of proteasomes in prion and other neurodegenerative diseases. The proteasome system may enhance its degradation activity by changing its structure, and this activity can also be increased by related chaperones when neuronal cells are subject to stress. When the proteasome system is inhibited, degradation of protein aggregates via autophagy may increase as a compensatory system. It is possible that a balance exists between the proteasome and autophagy in vivo; when one is impaired, the activity of the other may increase to maintain homeostasis. However, more studies are needed to elucidate the relationship between the proteasome system and autophagy.

KEYWORDS:

autophagy; neurodegenerative disease; prion disease; proteasome

PMID:
24829398
DOI:
10.1093/abbs/gmu031
[Indexed for MEDLINE]

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