Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Inhibition of the ubiquitin-proteasome system in Alzheimer's disease
Autore:
Lam, YA; Pickart, CM; Alban, A; Landon, M; Jamieson, C; Ramage, R; Mayer, RJ; Layfield, R;
Indirizzi:
Johns Hopkins Univ, Sch Publ Hlth, Dept Biochem, Baltimore, MD 21205 USA Johns Hopkins Univ Baltimore MD USA 21205 iochem, Baltimore, MD 21205 USA Univ Nottingham, Sch Med, Sch Biomed Sci, Queens Med Ctr, Nottingham NG7 2UH, England Univ Nottingham Nottingham England NG7 2UH , Nottingham NG7 2UH, England Univ Edinburgh, Dept Chem, Edinburgh EH9 3JJ, Midlothian, Scotland Univ Edinburgh Edinburgh Midlothian Scotland EH9 3JJ Midlothian, Scotland
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 18, volume: 97, anno: 2000,
pagine: 9902 - 9906
SICI:
0027-8424(20000829)97:18<9902:IOTUSI>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMYLOID PRECURSOR PROTEIN; POLYUBIQUITIN CHAINS; DEGRADATION SIGNAL; PRESENILIN-1; EXPRESSION; CELLS; DEFICIENCY; CLEAVAGE; ENZYMES; LYSINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Pickart, CM Johns Hopkins Univ, Dept Biochem & Mol Biol, Room 8041,615 N Wolfe St, Baltimore, MD 21205 USA Johns Hopkins Univ Room 8041,615 N Wolfe St Baltimore MD USA 21205
Citazione:
Y.A. Lam et al., "Inhibition of the ubiquitin-proteasome system in Alzheimer's disease", P NAS US, 97(18), 2000, pp. 9902-9906

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 withno 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/11/20 alle ore 05:51:55