Aß peptides and the exposure of their hydrophobic residues upon copper(ii) complex formation: probing mechanisms of amyloid plaque formation in human and rat peptide complexes

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Sarah Sipe (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Alzheimer’s Disease (AD) is a progressive, neurodegenerative disease that affects 35 million people worldwide and is the 6th leading cause of death in the United States. AD is characterized by neurofibrillary tangles and amyloid plaques in the brain. The plaques are formed when amyloid beta (Aß) peptides aggregate at their hydrophobic residues. Elevated concentrations of essential metals, copper, iron, and zinc, have been detected in the plaques and research indicates that the presence of metals speed up the formation of the plaques. Previous binding studies have determined that metal binding occurs within the first 16 amino acids of the Aß peptide, which can be either 40 or 42 amino acids long. The rat Aß peptide differs by only three amino acid point substitutions and are immune to aggregation. Based on previous thermodynamic binding studies, the exposure of the peptides’ hydrophobic residues when bound to copper (II) are hypothesized to be more exposed in the human peptide than the rat. To test this hypothesis, rat and human Aß28 peptides are probed with hydrophobic fluorophore 1,8-ANS. Increased fluorescence is expected of human Aß28 if the hydrophobic residues of the peptide-copper complexes are indeed more exposed.

Additional Information

Publication

Honors Project

Sipe, Sarah. (2015). Aß peptides and the exposure of their hydrophobic residues upon copper(ii) complex formation: probing mechanisms of amyloid plaque formation in human and rat peptide complexes. Unpublished manuscript, Honors College, East Carolina Un

Language: English

Date: 2015

Keywords

Fluorometry, Amyloid-ß, Alzheimer's disease, Amyloid beta

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