| dc.identifier.uri | http://hdl.handle.net/11401/77158 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | Amyloid fibrils are insoluble protein aggregates found in organs and tissues, and are structurally dominated by β -strands. Amyloid formation has been implicated in a wide range of human diseases. Each disease is characterized by a specific protein or peptide that aggregates in certain conditions. For example, the amyloid β protein (Aβ ) forms amyloid plaques in the brain of patients with Alzheimer's disease and this leads to neuronal degeneration. Parkinson's disease, another common neurodegenerative disorder, is associated with the intracellular aggregation of alpha-synuclein to form Lewy bodies in the brains of patients. This dissertation focuses on a polypeptide hormone, human islet amyloid polypeptide (IAPP, also known as amylin), which is co-secreted with insulin from pancreatic β -cells and forms islet amyloid deposits in type 2 diabetes. Although several models of IAPP aggregation have been proposed and inhibitors of amyloid formation have been developed, the mechanism of amyloid formation by IAPP is still not known. In this dissertation, the role of aromatic interaction was examined by mutational analysis of a series of Phe to Leu mutants. We also investigated the role of the C-terminus of IAPP and its interaction with His-18 during amyloid formation by IAPP. Several potential inhibitors of IAPP amyloid formation including the non-steroid anti-inflammatory drugs, Aspirin and Ketoprofen, and the red wine ingredient, Resveratrol were tested. In addition, we characterized Matrix Metallopeptidase 9 (MMP 9) IAPP cleavage products to better understand how this protease regulates IAPP amyloid formation. These studies aim to provide new insights into the mechanism of IAPP aggregation and the screening of inhibitors. | |
| dcterms.available | 2017-09-20T16:52:07Z | |
| dcterms.contributor | Simmerling, Carlos | en_US |
| dcterms.contributor | Raleigh, Daniel P | en_US |
| dcterms.contributor | Boon, Elizabeth | en_US |
| dcterms.contributor | de los Santos, Carlos. | en_US |
| dcterms.creator | Tu, Ling-Hsien | |
| dcterms.dateAccepted | 2017-09-20T16:52:07Z | |
| dcterms.dateSubmitted | 2017-09-20T16:52:07Z | |
| dcterms.description | Department of Chemistry. | en_US |
| dcterms.extent | 206 pg. | en_US |
| dcterms.format | Application/PDF | en_US |
| dcterms.format | Monograph | |
| dcterms.identifier | http://hdl.handle.net/11401/77158 | |
| dcterms.issued | 2015-08-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:52:07Z (GMT). No. of bitstreams: 1
Tu_grad.sunysb_0771E_11941.pdf: 8178119 bytes, checksum: fd7590981d4448a67f108bb042aef9d1 (MD5)
Previous issue date: 2014 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Chemistry | |
| dcterms.title | Formation and Inhibition of Islet Amyloid in Type 2 Diabetes | |
| dcterms.type | Dissertation | |
