Academic Journal
Amyloid-β peptide binds to cytochrome C oxidase subunit 1.
العنوان: | Amyloid-β peptide binds to cytochrome C oxidase subunit 1. |
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المؤلفون: | Luis Fernando Hernandez-Zimbron, Jose Luna-Muñoz, Raul Mena, Ricardo Vazquez-Ramirez, Carlos Kubli-Garfias, David H Cribbs, Karen Manoutcharian, Goar Gevorkian |
المصدر: | PLoS ONE, Vol 7, Iss 8, p e42344 (2012) |
بيانات النشر: | Public Library of Science (PLoS), 2012. |
سنة النشر: | 2012 |
المجموعة: | LCC:Medicine LCC:Science |
مصطلحات موضوعية: | Medicine, Science |
الوصف: | Extracellular and intraneuronal accumulation of amyloid-beta aggregates has been demonstrated to be involved in the pathogenesis of Alzheimer's disease (AD). However, the precise mechanism of amyloid-beta neurotoxicity is not completely understood. Previous studies suggest that binding of amyloid-beta to a number of macromolecules has deleterious effects on cellular functions. Mitochondria were found to be the target for amyloid-beta, and mitochondrial dysfunction is well documented in AD. In the present study we have shown for the first time that Aβ 1-42 bound to a peptide comprising the amino-terminal region of cytochrome c oxidase subunit 1. Phage clone, selected after screening of a human brain cDNA library expressed on M13 phage and bearing a 61 amino acid fragment of cytochrome c oxidase subunit 1, bound to Aβ 1-42 in ELISA as well as to Aβ aggregates present in AD brain. Aβ 1-42 and cytochrome c oxidase subunit 1 co-immunoprecipitated from mitochondrial fraction of differentiated human neuroblastoma cells. Likewise, molecular dynamics simulation of the cytochrome c oxidase subunit 1 and the Aβ 1-42 peptide complex resulted in a reliable helix-helix interaction, supporting the experimental results. The interaction between Aβ 1-42 and cytochrome c oxidase subunit 1 may explain, in part, the diminished enzymatic activity of respiratory chain complex IV and subsequent neuronal metabolic dysfunction observed in AD. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1932-6203 |
Relation: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22927926/?tool=EBI; https://doaj.org/toc/1932-6203 |
DOI: | 10.1371/journal.pone.0042344 |
URL الوصول: | https://doaj.org/article/fff283e4831e4f22be5c18ec56fddbbe |
رقم الانضمام: | edsdoj.fff283e4831e4f22be5c18ec56fddbbe |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 19326203 |
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DOI: | 10.1371/journal.pone.0042344 |