Amyloid-β peptide binds to cytochrome C oxidase subunit 1.
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 amylo...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22927926/?tool=EBI |
| _version_ | 1818435241354723328 |
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| author | Luis Fernando Hernandez-Zimbron Jose Luna-Muñoz Raul Mena Ricardo Vazquez-Ramirez Carlos Kubli-Garfias David H Cribbs Karen Manoutcharian Goar Gevorkian |
| author_facet | Luis Fernando Hernandez-Zimbron Jose Luna-Muñoz Raul Mena Ricardo Vazquez-Ramirez Carlos Kubli-Garfias David H Cribbs Karen Manoutcharian Goar Gevorkian |
| author_sort | Luis Fernando Hernandez-Zimbron |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T16:49:45Z |
| format | Article |
| id | doaj.art-fff283e4831e4f22be5c18ec56fddbbe |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T16:49:45Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-fff283e4831e4f22be5c18ec56fddbbe2022-12-21T22:54:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4234410.1371/journal.pone.0042344Amyloid-β peptide binds to cytochrome C oxidase subunit 1.Luis Fernando Hernandez-ZimbronJose Luna-MuñozRaul MenaRicardo Vazquez-RamirezCarlos Kubli-GarfiasDavid H CribbsKaren ManoutcharianGoar GevorkianExtracellular 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22927926/?tool=EBI |
| spellingShingle | Luis Fernando Hernandez-Zimbron Jose Luna-Muñoz Raul Mena Ricardo Vazquez-Ramirez Carlos Kubli-Garfias David H Cribbs Karen Manoutcharian Goar Gevorkian Amyloid-β peptide binds to cytochrome C oxidase subunit 1. PLoS ONE |
| title | Amyloid-β peptide binds to cytochrome C oxidase subunit 1. |
| title_full | Amyloid-β peptide binds to cytochrome C oxidase subunit 1. |
| title_fullStr | Amyloid-β peptide binds to cytochrome C oxidase subunit 1. |
| title_full_unstemmed | Amyloid-β peptide binds to cytochrome C oxidase subunit 1. |
| title_short | Amyloid-β peptide binds to cytochrome C oxidase subunit 1. |
| title_sort | amyloid β peptide binds to cytochrome c oxidase subunit 1 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22927926/?tool=EBI |
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