Amyloid beta peptide heterogeneity studied by limited proteolysis / by Ryan Patrick Murray.

Author/creator Murray, Ryan Patrick author.
Other author Teller, Jan K., degree supervisor.
Other author Kalmus, Gerhard W., degree supervisor.
Other author East Carolina University. Department of Biology.
Format Theses and dissertations
Production2006.
Description137 leaves : illustrations ; 28 cm
Supplemental ContentAccess via ScholarShip
Subjects

Summary Alzheimer's disease (AD) results in a progressive decline in memory and cognitive abilities, consequently leading to dementia. Hallmarks of AD are dramatic loss in brain mass, due to neurodegeneration, and the appearance of amyloid plaques. The extracellular amyloid plaques accumulate throughout the cortex exerting toxic effects upon the local neuronal and glial cell populations. The initiation of these formations is caused by the aggregation of Amyloid Beta (A[beta]) peptides. These peptides are cleavage products of the ubiquitously expressed, transmembrane Amyloid Precursor Protein (APP). It has been well established that A[beta] peptides are produced from this protein by the secretory enzymes: alpha-secretase, beta-secretase and gamma-secretase. The plaque lesions display a high degree of A[beta] peptide heterogeneity, though it is widely believed that the primary ]constituent of AD plaques is the A[beta] 1-42 peptide. However, there is evidence exhibiting that A[beta] heterogeneity is an inherent result of secretory pathway processing. It is also clear that parenchymal A[beta] is further proteolytically digested. Unknown to this point is whether the heterogeneity displayed in the human AD brain is a result of the secretory pathway alone, or if subsequent proteolysis is required to complete the process. The results of this work show that limited proteolysis of synthetic A[beta] peptides in their soluble and fibril forms does not result in the production of peptide fragments that correspond to the in vivo AD brain. However, consistent cleavage at the +11 amino acid residue in each.
General notePresented to the faculty of the Department of Biology.
General noteAdvisor: Jan K. Teller
General noteAdvisor: Gerhard W. Kalmus
Dissertation noteM.S. East Carolina University 2006
Bibliography noteIncludes bibliographical references (leaves 134)-137).
Genre/formdissertations.
Genre/formAcademic theses.
Genre/formAcademic theses.
Genre/formThèses et écrits académiques.

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