Generation of amyloid β protein from a presenilin-1 and βAPP complex

Presenilin-1 (PS1) is a causative gene in early onset familial Alzheimer’s disease (FAD). FAD-linked mutant PS1s significantly increased Aβ40 and Aβ42(43) levels (P < 0.001) and decreased the production of an 11.4 kD (β-stub) and an 8.7 kD (α-stub) carboxyl-terminal fragment of amyloid β precurso...

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Guardado en:
Detalles Bibliográficos
Publicado: 2002
Materias:
Aβ40
Aβ42(43)
Presenilin-1
PS1/βAPP complex
βAPP
γ-secretase
3 [(3 cholamidopropyl)dimethylammonio] 1 propanesulfonic acid
amyloid beta protein
enzyme inhibitor
gamma secretase
mutant protein
presenilin 1
protein precursor
Alzheimer disease
amino terminal sequence
article
carboxy terminal sequence
cell line
cell lysate
pathogenesis
pH
precipitation
priority journal
protein analysis
protein degradation
protein isolation
reaction analysis
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0006291X_v292_n2_p571_ShizukaIkeda
http://hdl.handle.net/20.500.12110/paper_0006291X_v292_n2_p571_ShizukaIkeda
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:Presenilin-1 (PS1) is a causative gene in early onset familial Alzheimer’s disease (FAD). FAD-linked mutant PS1s significantly increased Aβ40 and Aβ42(43) levels (P < 0.001) and decreased the production of an 11.4 kD (β-stub) and an 8.7 kD (α-stub) carboxyl-terminal fragment of amyloid β precursor protein (βAPP-CTFs) (P < 0.01). In the 2% CHAPS extracted lysates, the complex containing the amino-terminal fragment of PS1 (PS1-NTF), the carboxyl-terminal fragments of PS1 (PS1-CTF), and βAPP-CTFs was identified. Incubation of this isolated complex at pH 6.4 showed the direct generation of Aβ40 and γ-stub from this complex. This reaction was inhibited by a β-secretase inhibitor. The degrading rate of a co-precipitated β-stub was facilitated under the presence of FAD-linked mutant PS1s. This findings suggest that the direct generation of Aβ from the complex may play an important role in the pathogenesis of Alzheimer’s disease. © 2002 Elsevier Science (USA).

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