| dc.identifier.uri | http://hdl.handle.net/11401/77162 | |
| 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 formation, the aggregation of normally soluble proteins or polypeptides into highly ordered beta-sheet structures, is a characteristic feature of many human diseases including Alzheimer's disease, Parkinson's disease and type 2 diabetes. I centered my research on islet amyloid polypeptide (IAPP), a neuroendocrine hormone that forms fibrillar amyloid deposits in the extracellular space of the pancreatic islets of Langerhans in type 2 diabetes. Although whether IAPP amyloid formation is a cause or consequence of the disease is controversial, the aggregation process has been shown to induce beta-cell apoptosis and reduce beta-cell mass, which is a hallmark feature of type 2 diabetes. The mechanism of islet amyloid formation is not understood yet. Moreover, although there are some reported IAPP amyloid inhibitors, either peptide-based or small-molecule, lack of the clear modes of their actions impedes further development and their clinical use. A better understanding of the amyloidsis and inhibition mechanism could help explain the pathogenesis of type 2 diabetes and could lead to improved treatment for the disease. My work included a study of the effects of glycosaminoglycans, the main component of extracellular matrix which was believed to play a role in in vivo islet amyloid initiation and progression, on in vitro amyloid formation and inhibition; an investigation of the possible role of impaired proIAPP processing in islet amyloid formation; a rational design of several IAPP analogs with better solubility at neutral pH than a FDA approved drug, promising better adjunct drug candidates to insulin therapy for diabetes patients; a study to elucidate the factors which lead to optimum peptide based inhibitors of IAPP amyloid formation by examining the ability of a set of designed polypeptide analogs of IAPP; a critical examination of the inhibition of IAPP amyloid formation by inositol. | |
| dcterms.available | 2017-09-20T16:52:07Z | |
| dcterms.contributor | Wang, Jin | en_US |
| dcterms.contributor | Raleigh, Daniel P | en_US |
| dcterms.contributor | Lauher, Joseph | en_US |
| dcterms.contributor | Seeliger, Markus. | en_US |
| dcterms.creator | Wang, Hui | |
| dcterms.dateAccepted | 2017-09-20T16:52:07Z | |
| dcterms.dateSubmitted | 2017-09-20T16:52:07Z | |
| dcterms.description | Department of Chemistry. | en_US |
| dcterms.extent | 216 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.format | Application/PDF | en_US |
| dcterms.identifier | http://hdl.handle.net/11401/77162 | |
| dcterms.issued | 2014-12-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:52:07Z (GMT). No. of bitstreams: 1
Wang_grad.sunysb_0771E_11876.pdf: 9452021 bytes, checksum: 2f92cd2961af6a6e338787a3085ccf40 (MD5)
Previous issue date: 1 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Biochemistry | |
| dcterms.subject | amylin, amyloid, IAPP | |
| dcterms.title | Biophysical Insights into the Initiation and Inhibition of Amyloid Formation by Islet Amyloid Polypeptide | |
| dcterms.type | Dissertation | |
