Inhibition of the ubiquitin-proteasome system in Alzheimer's disease

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ID: 271030
2000
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Abstract
Alzheimer's disease is the most common cause of dementia in the elderly. Although several genetic defects have been identified in patients with a family history of this disease, the majority of cases involve individuals with no known genetic predisposition. A mutant form of ubiquitin, termed Ub(+1), has been selectively observed in the brains of Alzheimer's patients, including those with nonfamilial Alzheimer's disease, but it has been unclear why Ub(+1) expression should be deleterious. Here we show that Ub(+1) is an efficient substrate for polyubiquitination in vitro and in transfected human cells. The resulting polyubiquitin chains are refractory to disassembly by deubiquitinating enzymes and potently inhibit the degradation of a polyubiquitinated substrate by purified 26S proteasomes. Thus, expression of Ub(+1) in aging brain could result in dominant inhibition of the Ub-proteasome system, leading to neuropathologic consequences.
Reference Key
layfield2000proceedingsinhibition Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Y. A. Lam,C. M. Pickart,A. Alban,M. Landon,C. Jamieson,R. Ramage,R. J. Mayer,Robert Layfield;Y. A. Lam;C. M. Pickart;A. Alban;M. Landon;C. Jamieson;R. Ramage;R. J. Mayer;Robert Layfield;
Journal proceedings of the national academy of sciences
Year 2000
DOI
10.1073/pnas.170173897
URL
https://sciprofiles.com/publication/view/4cf18a25c157213c1664eff213a82c47
Keywords
proteasome alzheimer's disease brains polyubiquitinated substrate polyubiquitination inhibit

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