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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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_0006291X_v292_n2_p571_ShizukaIkeda |
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todo:paper_0006291X_v292_n2_p571_ShizukaIkeda2023-10-03T14:03:49Z Generation of amyloid β protein from a presenilin-1 and βAPP complex Shizuka-Ikeda, M. Matsubara, E. Ikeda, M. Kanai, M. Tomidokoro, Y. Ikeda, Y. Watanabe, M. Kawarabayashi, T. Harigaya, Y. Okamoto, K. Shoji, M. Maruyama, K. Castao, E.M. St. George-Hyslop, P. 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 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). JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_0006291X_v292_n2_p571_ShizukaIkeda |
| institution |
Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Shizuka-Ikeda, M. Matsubara, E. Ikeda, M. Kanai, M. Tomidokoro, Y. Ikeda, Y. Watanabe, M. Kawarabayashi, T. Harigaya, Y. Okamoto, K. Shoji, M. Maruyama, K. Castao, E.M. St. George-Hyslop, P. Generation of amyloid β protein from a presenilin-1 and βAPP complex |
| topic_facet |
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 |
| description |
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). |
| format |
JOUR |
| author |
Shizuka-Ikeda, M. Matsubara, E. Ikeda, M. Kanai, M. Tomidokoro, Y. Ikeda, Y. Watanabe, M. Kawarabayashi, T. Harigaya, Y. Okamoto, K. Shoji, M. Maruyama, K. Castao, E.M. St. George-Hyslop, P. |
| author_facet |
Shizuka-Ikeda, M. Matsubara, E. Ikeda, M. Kanai, M. Tomidokoro, Y. Ikeda, Y. Watanabe, M. Kawarabayashi, T. Harigaya, Y. Okamoto, K. Shoji, M. Maruyama, K. Castao, E.M. St. George-Hyslop, P. |
| author_sort |
Shizuka-Ikeda, M. |
| title |
Generation of amyloid β protein from a presenilin-1 and βAPP complex |
| title_short |
Generation of amyloid β protein from a presenilin-1 and βAPP complex |
| title_full |
Generation of amyloid β protein from a presenilin-1 and βAPP complex |
| title_fullStr |
Generation of amyloid β protein from a presenilin-1 and βAPP complex |
| title_full_unstemmed |
Generation of amyloid β protein from a presenilin-1 and βAPP complex |
| title_sort |
generation of amyloid β protein from a presenilin-1 and βapp complex |
| url |
http://hdl.handle.net/20.500.12110/paper_0006291X_v292_n2_p571_ShizukaIkeda |
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