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Titolo:
Pathogenic APP mutations near the gamma-secretase cleavage site differentially affect A beta secretion and APP C-terminal fragment stability
Autore:
De Jonghe, C; Esselens, C; Kumar-Singh, S; Craessaerts, K; Serneels, S; Checler, F; Annaert, W; Van Broeckhoven, C; De Strooper, B;
Indirizzi:
Univ Antwerp, Flanders Interuniv Inst Biotechnol, Dept Mol Genet, Neurogenet Lab, B-2020 Antwerp, Belgium Univ Antwerp Antwerp Belgium B-2020 rogenet Lab, B-2020 Antwerp, Belgium Katholieke Univ Leuven, Flanders Interuniv Inst Biotechnol, Dept Human Genet, Lab Neuronal Cell Biol, B-3000 Louvain, Belgium Katholieke Univ LeuvenLouvain Belgium B-3000 l, B-3000 Louvain, Belgium CNRS, Inst Pharmacol Mol & Cellulaire, F-06560 Valbonne, France CNRS Valbonne France F-06560 Mol & Cellulaire, F-06560 Valbonne, France
Titolo Testata:
HUMAN MOLECULAR GENETICS
fascicolo: 16, volume: 10, anno: 2001,
pagine: 1665 - 1671
SICI:
0964-6906(20010801)10:16<1665:PAMNTG>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMYLOID PRECURSOR PROTEIN; FAMILIAL ALZHEIMERS-DISEASE; AGE-OF-ONSET; HIPPOCAMPAL-NEURONS; MISSENSE MUTATION; APOE GENOTYPE; CELL-LINES; PRESENILIN-1; GENE; INCREASES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: De Strooper, B Univ Antwerp, Flanders Interuniv Inst Biotechnol, Dept Mol Genet, Neurogenet Lab, B-2020 Antwerp, Belgium Univ Antwerp Antwerp Belgium B-2020 2020 Antwerp, Belgium
Citazione:
C. De Jonghe et al., "Pathogenic APP mutations near the gamma-secretase cleavage site differentially affect A beta secretion and APP C-terminal fragment stability", HUM MOL GEN, 10(16), 2001, pp. 1665-1671

Abstract

Release of amyloid beta (A beta) from the amyloid precursor protein (APP) requires cleavages by beta- and gamma -secretases and plays a crucial role in Alzheimer's disease (AD) pathogenesis. Missense mutations in the APP gene causing familial AD are clustered around the beta-, alpha- and particulargamma -secretase cleavage sites. We systematically compare in primary neurons the effect on APP processing of a series of clinical APP mutations (twoof which not characterized before) located in close proximity to the gamma-secretase cleavage site. We confirm and extend previous observations showing that all these mutations (T714I, V715M, V715A, I716V, V717I and V717L) affect gamma -secretase cleavage causing an increased relative ratio of A beta 42 to A beta 40. Taking advantage of these extended series of APP mutations we were able to demonstrate an inverse correlation between these ratios and the age at onset of the disease in the different families In addition, a subset of mutations caused the accumulation of APP C-terminal fragmentsindicating that these mutations also influence the stability of APP C-terminal fragments. However, it is unlikely that these fragments contribute significantly to the disease process.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 18:50:48