Structure and assembly mechanisms of toxic human islet amyloid polypeptide oligomers associated with copper
نویسندگان
چکیده
Department of Chemistry, Ulsan Nationa (UNIST), Ulsan 44919, Republic of Korea. E Department of Chemistry, Pohang Universit Pohang 37673, Republic of Korea Department of Chemistry, Research Institu Seoul 02841, Republic of Korea. E-mail: hug Graduate School of Medical Life Science, Kanagawa 230-0045, Japan † Electronic supplementary information Fig. S1–S18 and Tables S1 and S2. See DO ‡ These authors equally contributed to th Cite this: Chem. Sci., 2016, 7, 5398
منابع مشابه
Causative factors for formation of toxic islet amyloid polypeptide oligomer in type 2 diabetes mellitus
Human islet amyloid polypeptide (h-IAPP) is a peptide hormone that is synthesized and cosecreted with insulin from insulin-secreting pancreatic β-cells. Recently, h-IAPP was proposed to be the main component responsible for the cytotoxic pancreatic amyloid deposits in patients with type 2 diabetes mellitus (T2DM). Since the causative factors of IAPP (or amylin) oligomer aggregation are not full...
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OBJECTIVE—Islets in type 2 diabetes are characterized by a deficit in -cells, increased -cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). The toxic form of amyloidogenic protein oligomers are distinct and smaller than amyloid fibrils and act by disrupting membranes. Using antibodies that bind to toxic IAPP oligomers (but not IAPP monomers or fibrils) and a vaccin...
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Background: Type 2 diabetes (T2D) is a chronic metabolic disorder in which beta-cells are destroyed. The islet amyloid polypeptide (IAPP) produced by beta-cells has been reported to influence beta-cell destruction. Objective: To evaluate if IAPP can act as an autoantigen and therefore, to see if CD8 + T-cells specific for this protein might be present in T2D patients. Methods: Peripheral blood ...
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The precise molecular mechanisms by which different peptides and proteins assemble into highly ordered amyloid deposits remain elusive. The fibrillation of human amylin (also known as islet amyloid polypeptide, hIAPP) and the amyloid-beta peptide (Aβ-40) are thought to be pathogenic factors in Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD), respectively. Amyloid diseases may invol...
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The human islet amyloid polypeptide (hIAPP) is the primary component in the toxic islet amyloid deposits in type-2 diabetes. hIAPP self-assembles to aggregates that permeabilize membranes and constitutes amyloid plaques. Uncovering the mechanisms of amyloid self-assembly is the key to understanding amyloid toxicity and treatment. Although structurally similar, hIAPP's rat counterpart, the rat i...
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