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Copper binding to the Alzheimer’s disease amyloid precursor protein
Alzheimer’s disease is the fourth biggest killer in developed countries. Amyloid precursor protein (APP) plays a central role in the development of the disease, through the generation of a peptide called Aβ by proteolysis of the precursor protein. APP can function as a metalloprotein and modulate co...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Springer-Verlag
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921068/ https://www.ncbi.nlm.nih.gov/pubmed/18030462 http://dx.doi.org/10.1007/s00249-007-0234-3 |
Sumario: | Alzheimer’s disease is the fourth biggest killer in developed countries. Amyloid precursor protein (APP) plays a central role in the development of the disease, through the generation of a peptide called Aβ by proteolysis of the precursor protein. APP can function as a metalloprotein and modulate copper transport via its extracellular copper binding domain (CuBD). Copper binding to this domain has been shown to reduce Aβ levels and hence a molecular understanding of the interaction between metal and protein could lead to the development of novel therapeutics to treat the disease. We have recently determined the three-dimensional structures of apo and copper bound forms of CuBD. The structures provide a mechanism by which CuBD could readily transfer copper ions to other proteins. Importantly, the lack of significant conformational changes to CuBD on copper binding suggests a model in which copper binding affects the dimerisation state of APP leading to reduction in Aβ production. We thus predict that disruption of APP dimers may be a novel therapeutic approach to treat Alzheimer’s disease. |
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