Prions and the proteasome

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1782

Review

Deriziotis, Pelagia¹  Tabrizi, Sarah J.¹ 

[1] UCL, Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England

关键词: Prion disease;    Ubiquitin proteasome system;    Cytosolic PrPc;    Aggresomes;    Oligomers;    Toxicity;   

DOI  :  10.1016/j.bbadis.2008.06.011

来源: Elsevier

【 摘 要 】

Prion diseases are fatal neurodegenerative disorders that include Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in animals. They are unique in terms of their biology because they are Caused by the conformational re-arrangement of a normal host-encoded prion protein, PrPC, to all abnormal infectious isoform, PrPC. Currently the precise mechanism behind prion-mediated neurodegeneration remains Unclear. It is hypothesised than an Unknown toxic gain Of function of PrPSc, or an intermediate oligomeric form, underlies neuronal death. Increasing evidence Suggests a role for the ubiquitin proteasome system (UPS) in prion disease. Both wild-type PrPC and disease-associated PrP isoforms accumulate in cells after proteasome inhibition leading to increased cell death, and abnormal beta-sheet-rich PrP isoforms have been shown to inhibit the catalytic activity of the proteasome. Here we review potential interactions between priors and the proteasome outlining how the UPS may be implicated in prion-mediated neurodegeneration. (C) 2008 Elsevier B.V. All rights reserved.

【 授权许可】

Free