التفاصيل البيبلوغرافية
| العنوان: |
Binding of longer Aβ to transmembrane domain 1 of presenilin 1 impacts on Aβ42 generation |
| المؤلفون: |
Ohki, Yu, Shimada, Naoaki, Tominaga, Aya, Osawa, Satoko, Higo, Takuya, Yokoshima, Satoshi, Fukuyama, Tohru, Tomita, Taisuke, Iwatsubo, Takeshi |
| بيانات النشر: |
BioMed Central Ltd. |
| سنة النشر: |
2014 |
| المجموعة: |
BioMed Central |
| مصطلحات موضوعية: |
Presenilin, Secretases, Alzheimer disease, Intramembrane proteolysis, γ-Secretase modulator |
| الوصف: |
Background Amyloid-β peptide ending at 42nd residue (Aβ42) is believed as a pathogenic peptide for Alzheimer disease. Although γ-secretase is a responsible protease to generate Aβ through a processive cleavage, the proteolytic mechanism of γ-secretase at molecular level is poorly understood. Results We found that the transmembrane domain (TMD) 1 of presenilin (PS) 1, a catalytic subunit for the γ-secretase, as a key modulatory domain for Aβ42 production. Aβ42-lowering and -raising γ-secretase modulators (GSMs) directly targeted TMD1 of PS1 and affected its structure. A point mutation in TMD1 caused an aberrant secretion of longer Aβ species including Aβ45 that are the precursor of Aβ42. We further found that the helical surface of TMD1 is involved in the binding of Aβ45/48 and that the binding was altered by GSMs as well as TMD1 mutation. Conclusions Binding between PS1 TMD1 and longer Aβ is critical for Aβ42 production. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| Relation: |
http://www.molecularneurodegeneration.com/content/9/1/7 |
| الاتاحة: |
http://www.molecularneurodegeneration.com/content/9/1/7 |
| Rights: |
Copyright 2014 Ohki et al.; licensee BioMed Central Ltd. |
| رقم الانضمام: |
edsbas.B49EBD6B |
| قاعدة البيانات: |
BASE |