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Titolo:
Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct
Autore:
Conway, KA; Rochet, JC; Bieganski, RM; Lansbury, PT;
Indirizzi:
Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Cambridge, MA 02139 USA Harvard Univ Cambridge MA USA 02139 r Neurol Dis, Cambridge, MA 02139 USA
Titolo Testata:
SCIENCE
fascicolo: 5545, volume: 294, anno: 2001,
pagine: 1346 - 1349
SICI:
0036-8075(20011109)294:5545<1346:KSOTAP>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; LEWY BODIES; FIBRILLIZATION; TOXICITY; MICE; LEVODOPA; MUTATION; MODEL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Agriculture,Biology & Environmental Sciences
Life Sciences
Physical, Chemical & Earth Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Lansbury, PT Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis,65 Landsdowne St, Cambridge, MA 02139 USA Harvard Univ 65 Landsdowne St Cambridge MA USA 02139 2139 USA
Citazione:
K.A. Conway et al., "Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct", SCIENCE, 294(5545), 2001, pp. 1346-1349

Abstract

The substantia nigra in Parkinson's disease (PD) is depleted of dopaminergic neurons and contains fibrillar Lewy bodies comprising primarily alpha -synuclein. We screened a library to identify drug-like molecules to probe the relation between neurodegeneration and alpha -synuctein fibrilization. All but one of 15 fibril inhibitors were catecholamines related to dopamine. The inhibitory activity of dopamine depended on its oxidative ligation to alpha -synuctein and was selective for the protofibril-to-fibril conversion,causing accumulation of the alpha -synuctein protofibril. Adduct formationprovides an explanation for the dopaminergic selectivity of alpha -synuctein-associated neurotoxicity in PD and has implications for current and future PD therapeutic and diagnostic strategies.

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Documento generato il 11/07/20 alle ore 17:21:36