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Titolo:
gamma-secretase inhibitors as molecular probes of presenilin function
Autore:
Wolfe, MS;
Indirizzi:
Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA Brigham & Womens Hosp Boston MA USA 02115 eurol Dis, Boston, MA 02115 USA Harvard Univ, Sch Med, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 vard Univ, Sch Med, Boston, MA 02115 USA
Titolo Testata:
JOURNAL OF MOLECULAR NEUROSCIENCE
fascicolo: 2, volume: 17, anno: 2001,
pagine: 199 - 204
SICI:
0895-8696(200110)17:2<199:GIAMPO>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
FAMILIAL ALZHEIMERS-DISEASE; AMYLOID PRECURSOR PROTEIN; CAENORHABDITIS-ELEGANS; INTRACELLULAR DOMAIN; MISSENSE MUTATIONS; ASPARTYL PROTEASE; BETA-PROTEIN; STATE; ENDOPROTEOLYSIS; GENE;
Keywords:
Alzheimer's disease; amyloid; amyloid precursor protein; Notch; protease;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Wolfe, MS Brigham & Womens Hosp, Ctr Neurol Dis, 77 Ave Louis Pasteur,HIM 626, Boston, MA 02115 USA Brigham & Womens Hosp 77 Ave Louis Pasteur,HIM 626 Boston MA USA 02115
Citazione:
M.S. Wolfe, "gamma-secretase inhibitors as molecular probes of presenilin function", J MOL NEURO, 17(2), 2001, pp. 199-204

Abstract

Mutations in the presenilins cause Alzheimer's disease (AD) and alter gamma -secretase activity to increase the production of the 42-residue amyloid-beta peptide (A beta) found disproportionally in the cerebral plaques that characterize the disease. The serpentine presenilins are required for transmembrane cleavage of both the amyloid-P precursor protein (APP) and the Notch receptor by gamma -secretase, and presenilins are biochemically associated with the protease. Inhibitors of gamma -secretase have provided criticalclues to the function of presenilins. Pharmacological profiling suggested that gamma -secretase is an aspartyl protease, leading to the identification of two conserved aspartates important to presenilin's role in proteolysis. Conversion of transition-state analogue inhibitors of gamma -secretase toaffinity reagents resulted in specific tagging of the heterodimeric form of presenilins, strongly suggesting that the active site of gamma -secretaselies at the interface of the presenilin heterodimer. Heterodimeric presenilin appears to be the catalytic portion of a multi-protein gamma -secretasecomplex.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 03:20:52