scholarly journals Influence of Aluminium and EGCG on Fibrillation and Aggregation of Human Islet Amyloid Polypeptide

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Zhi-Xue Xu ◽  
Qiang Zhang ◽  
Gong-Li Ma ◽  
Cong-Heng Chen ◽  
Yan-Ming He ◽  
...  
Keyword(s):  
Type Ii Diabetes ◽  
Islet Amyloid Polypeptide ◽  
Epigallocatechin Gallate ◽  
Inhibitory Effect ◽  
Human Islet ◽  
Molar Ratio ◽  
Type Ii ◽  
Amyloid Proteins ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide

The abnormal fibrillation of human islet amyloid polypeptide (hIAPP) has been implicated in the development of type II diabetes. Aluminum is known to trigger the structural transformation of many amyloid proteins and induce the formation of toxic aggregate species. The (−)-epigallocatechin gallate (EGCG) is considered capable of binding both metal ions and amyloid proteins with inhibitory effect on the fibrillation of amyloid proteins. However, the effect of Al(III)/EGCG complex on hIAPP fibrillation is unclear. In the present work, we sought to view insight into the structures and properties of Al(III) and EGCG complex by using spectroscopic experiments and quantum chemical calculations and also investigated the influence of Al(III) and EGCG on hIAPP fibrillation and aggregation as well as their combined interference on this process. Our studies demonstrated that Al(III) could promote fibrillation and aggregation of hIAPP, while EGCG could inhibit the fibrillation of hIAPP and lead to the formation of hIAPP amorphous aggregates instead of the ordered fibrils. Furthermore, we proved that the Al(III)/EGCG complex in molar ratio of 1 : 1 as Al(EGCG)(H2O)2 could inhibit the hIAPP fibrillation more effectively than EGCG alone. The results provide the invaluable reference for the new drug development to treat type II diabetes.

scholarly journals γ-AApeptides–based Small Molecule Ligands That Disaggregate Human Islet Amyloid Polypeptide

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Olapeju Bolarinwa ◽  
Chunpu Li ◽  
Nawal Khadka ◽  
Qi Li ◽  
Yan Wang ◽  
...  
Keyword(s):  
Type Ii Diabetes ◽  
Islet Amyloid Polypeptide ◽  
Typical Feature ◽  
Human Islet ◽  
Type Ii ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide ◽  
Age Related ◽  
Small Molecule Ligands ◽  
Human Amylin

AbstractThe abnormal folding and aggregation of functional proteins into amyloid is a typical feature of many age-related diseases, including Type II diabetes. Growing evidence has revealed that the prevention of aggregate formation in culprit proteins could retard the progression of amyloid diseases. Human Amylin, also known as human islet amyloid polypeptide (hIAPP), is the major factor for categorizing Type II diabetes as an amyloid disease. Specifically, hIAPP has a great aggregation potential, which always results in a lethal situation for the pancreas. Many peptide inhibitors have been constructed from the various segments of the full-length hIAPP peptide; however, only a few have their origin from the screening of combinatorial peptidomimetic library. In this study, based on HW-155, which was previously discovered from a one–bead–one compound (OBOC) library to inhibit Aβ40 aggregation, we investigated eight (8) analogues and evaluated their amyloid-prevention capabilities for inhibiting fibrillization of hIAPP. Characterization studies revealed that all analogues of HW-155, as well as HW-155, were effective inhibitors of the fibril formation by hIAPP.

scholarly journals Brazilin inhibits fibrillogenesis of human islet amyloid polypeptide, disassembles mature fibrils, and alleviates cytotoxicity

RSC Advances ◽  
2017 ◽  
Vol 7 (69) ◽  
pp. 43491-43501 ◽  
Author(s):  
Jingjing Guo ◽  
Wanqi Sun ◽  
Li Li ◽  
Fufeng Liu ◽  
Wenyu Lu
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Simulation ◽  
Type Ii Diabetes ◽  
Islet Amyloid Polypeptide ◽  
Type Ii Diabetes Mellitus ◽  
Inhibitory Effect ◽  
Human Islet ◽  
Type Ii ◽  
Islet Amyloid ◽  
Simulation Experiments

Inhibitory effect of brazilin on the fibrillogenesis of hIAPP was explored using biochemical, biophysical, cytobiological and molecular simulation experiments. Brazilin was a potential compound for therapeutic treatment of type II diabetes mellitus.

scholarly journals Inhibition of IAPP Aggregation and Toxicity by Natural Products and Derivatives

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Amit Pithadia ◽  
Jeffrey R. Brender ◽  
Carol A. Fierke ◽  
Ayyalusamy Ramamoorthy
Keyword(s):  
Natural Products ◽  
Small Molecules ◽  
Type Ii Diabetes ◽  
Pancreatic Beta Cell ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Pathological Feature ◽  
Type Ii ◽  
Cell Toxicity ◽  
Islet Amyloid

Fibrillar aggregates of human islet amyloid polypeptide, hIAPP, a pathological feature seen in some diabetes patients, are a likely causative agent for pancreatic beta-cell toxicity, leading to a transition from a state of insulin resistance to type II diabetes through the loss of insulin producing beta-cells by hIAPP induced toxicity. Because of the probable link between hIAPP and the development of type II diabetes, there has been strong interest in developing reagents to study the aggregation of hIAPP and possible therapeutics to block its toxic effects. Natural products are a class of compounds with interesting pharmacological properties against amyloids which have made them interesting targets to study hIAPP. Specifically, the ability of polyphenolic natural products, EGCG, curcumin, and resveratrol, to modulate the aggregation of hIAPP is discussed. Furthermore, we have outlined possible mechanistic discoveries of the interaction of these small molecules with the peptide and how they may mitigate toxicity associated with peptide aggregation. These abundantly found agents have been long used to combat diseases for many years and may serve as useful templates toward developing therapeutics against hIAPP aggregation and toxicity.

scholarly journals Influence of a curcumin derivative on hIAPP aggregation in the absence and presence of lipid membranes

2016 ◽  
Vol 52 (5) ◽  
pp. 942-945 ◽  
Author(s):  
Amit S. Pithadia ◽  
Anirban Bhunia ◽  
Rajendran Sribalan ◽  
Vediappen Padmini ◽  
Carol A. Fierke ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Lipid Membranes ◽  
Type Ii Diabetes ◽  
Islet Amyloid Polypeptide ◽  
Type Ii Diabetes Mellitus ◽  
Human Islet ◽  
Type Ii ◽  
Β Cells ◽  
Islet Amyloid ◽  
Curcumin Derivative

The deposition of aggregates of human islet amyloid polypeptide (hIAPP) has been correlated with the death of β-cells in type II diabetes mellitus.

Inhibitory Mechanism of Epigallocatechin Gallate on Fibrillation and Aggregation of Amidated Human Islet Amyloid Polypeptide

ChemPhysChem ◽  
2017 ◽  
Vol 18 (12) ◽  
pp. 1611-1619 ◽  
Author(s):  
Zhi-Xue Xu ◽  
Gong-Li Ma ◽  
Qiang Zhang ◽  
Cong-Heng Chen ◽  
Yan-Ming He ◽  
...  
Keyword(s):  
Islet Amyloid Polypeptide ◽  
Epigallocatechin Gallate ◽  
Human Islet ◽  
Inhibitory Mechanism ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide

Human islet amyloid polypeptide accumulates at similar sites in islets of transgenic mice and humans

Diabetes ◽  
1994 ◽  
Vol 43 (5) ◽  
pp. 640-644 ◽  
Author(s):  
E. J. de Koning ◽  
J. W. Hoppener ◽  
J. S. Verbeek ◽  
C. Oosterwijk ◽  
K. L. van Hulst ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide

scholarly journals The flanking peptides issue from the maturation of the human islet amyloid polypeptide (hIAPP) slightly modulate hIAPP-fibril formation but not hIAPP-induced cell death

Biochimie ◽  
2020 ◽  
Vol 170 ◽  
pp. 26-35 ◽  
Author(s):  
Shadai Salazar Vazquez ◽  
Bertrand Blondeau ◽  
Pierre Cattan ◽  
Mathieu Armanet ◽  
Ghislaine Guillemain ◽  
...  
Keyword(s):  
Cell Death ◽  
Islet Amyloid Polypeptide ◽  
Fibril Formation ◽  
Human Islet ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide

scholarly journals Regulation of divalent metal ions to the aggregation and membrane damage of human islet amyloid polypeptide oligomers

RSC Advances ◽  
2021 ◽  
Vol 11 (21) ◽  
pp. 12815-12825
Author(s):  
Yajie Wang ◽  
Feihong Meng ◽  
Tong Lu ◽  
Chunyun Wang ◽  
Fei Li
Keyword(s):  
Metal Ions ◽  
Metal Binding ◽  
Membrane Damage ◽  
Islet Amyloid Polypeptide ◽  
Divalent Metal ◽  
Human Islet ◽  
Divalent Metal Ions ◽  
Islet Amyloid ◽  
Induced Membrane ◽  
Human Islet Amyloid Polypeptide

Their is a counteraction between a decrease in the disruptive ability of metal-associated oligomer species and an increase in the quantity of oligomers promoted by the metal binding in the activity of hIAPP induced membrane damage.

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