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Biophysical Insights into the Initiation and Inhibition of Amyloid Formation by Islet Amyloid Polypeptide

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dc.contributor.advisor Raleigh, Daniel P en_US
dc.contributor.author Wang, Hui en_US
dc.contributor.other Department of Chemistry. en_US
dc.date.accessioned 2017-09-20T16:52:07Z
dc.date.available 2017-09-20T16:52:07Z
dc.date.issued 2014-12-01 en_US
dc.identifier.uri http://hdl.handle.net/11401/77162 en_US
dc.description 216 pg. en_US
dc.description.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. en_US
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 en_US
dc.format.medium Electronic Resource en_US
dc.language.iso en_US en_US
dc.publisher The Graduate School, Stony Brook University: Stony Brook, NY. en_US
dc.subject.lcsh Biochemistry en_US
dc.subject.other amylin, amyloid, IAPP en_US
dc.title Biophysical Insights into the Initiation and Inhibition of Amyloid Formation by Islet Amyloid Polypeptide en_US
dc.type Dissertation en_US
dc.mimetype Application/PDF en_US
dc.contributor.committeemember Wang, Jin en_US
dc.contributor.committeemember Lauher, Joseph en_US
dc.contributor.committeemember Seeliger, Markus. en_US

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