Article
Biochemistry & Molecular Biology
Noe Quittot, Mathilde Fortier, Margaryta Babych, Phuong Trang Nguyen, Mathew Sebastiao, Steve Bourgault
Summary: The study reveals that GAGs exacerbate IAPP-induced cytotoxicity and membrane perturbation, increasing the local concentration of IAPP on the cell surface and promoting lipid bilayer disturbance and cell death.
Article
Biochemistry & Molecular Biology
Lucie Khemtemourian, Hebah Fatafta, Benoit Davion, Sophie Lecomte, Sabine Castano, Birgit Strodel
Summary: This study investigates the molecular details of IAPP binding to lipid membranes, revealing different membrane interaction modes and aggregation structures for different IAPP variants. Residue 18 plays a decisive role in the structure and membrane interaction of IAPP, making it a potential therapeutic target for inhibiting IAPP toxicity.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Cell Biology
Sofia Ferreira, Ana F. Raimundo, Regina Menezes, Ivo C. Martins
Summary: This study discusses the association of IAPP with diabetes, Aβ, and dementia, elucidating the pathological role of IAPP in AD. Research has shown that IAPP not only contributes to cognitive decline, but also harms the blood-brain barrier, interacts directly with Aβ, and co-deposits with it, leading to diabetes-associated dementia.
NEURAL REGENERATION RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Mathilde Fortier, Melanie Cote-Cyr, Vy Nguyen, Margaryta Babych, Phuong Trang Nguyen, Roger Gaudreault, Steve Bourgault
Summary: This study investigates the physicochemical and conformational properties driving the self-assembly of islet amyloid polypeptide (IAPP) and its associated cytotoxicity. It reveals the importance of the 12-17 hydrophobic region for self-recognition and identifies certain amino acids critical for amyloid fibril formation. Additionally, the study shows that modulating the peptide backbone flexibility at position Leu16 can inhibit amyloid formation and reduce cytotoxicity. These findings contribute to the development of therapeutic approaches for preventing IAPP aggregation.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Anns Mahboob, Degiri Kalana Lasanga Senevirathne, Pradipta Paul, Faisal Nabi, Rizwan Hasan Khan, Ali Chaari
Summary: Type 2 diabetes is a chronic metabolic disease with a significant global disease burden. Non-genetic risk factors for T2D include obesity, diet, physical activity, lifestyle, smoking, age, ethnicity, and mental stress. The aggregation and misfolding of hIAPP have detrimental effects on beta-cell function and health. Polyphenols have shown promising potential as natural therapeutics for inhibiting hIAPP aggregation and mitigating larger pathological effects of T2D, but further studies are needed to evaluate their mechanisms of action and ideal doses.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Agriculture, Multidisciplinary
Raliat O. Abioye, Ogadimma D. Okagu, Chibuike C. Udenigwe
Summary: The influence of 12 food-derived phenolic compounds on islet amyloid polypeptide (IAPP) fibrillation was investigated. The results showed that gallic acid, caffeic acid, and rutin and its aglycone, quercetin, can inhibit IAPP fibrillation at specific ratios, and rutin and quercetin can change the structural features of IAPP.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Raliat O. Abioye, Ogadimma D. Okagu, Chibuike C. Udenigwe
Summary: In this study, three tetrapeptides (TNGQ, MANT, and YMSV) were identified as inhibitors of IAPP fibrillation. Among them, TNGQ was the most effective inhibitor. Through a series of experiments and molecular docking simulation, we revealed the mechanism of TNGQ in inhibiting IAPP fibrillation and found that TNGQ may act by disaggregating preformed IAPP fibrils.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ye Wang, Joakim Bergstrom, Martin Ingelsson, Gunilla T. T. Westermark
Summary: This study investigates the interaction between alpha-synuclein (aSyn) and islet amyloid polypeptide (IAPP) in Alzheimer's disease and type 2 diabetes. The results show intracellular co-localization of aSyn with IAPP, but aSyn is absent in the extracellular amyloid deposits. In vitro experiments demonstrate that preformed aSyn fibrils can seed IAPP fibril formation, but IAPP does not affect aSyn fibrillation.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Hsiao-Chieh Tsai, Ching-Hong Huang, Ling-Hsien Tu
Summary: Islet amyloid polypeptide (IAPP) is a polypeptide hormone co-secreted with insulin by pancreatic beta-cells. It tends to aggregate into soluble oligomers, which are considered one of the hallmarks of type II diabetes. This study successfully grafted the aggregation-induced emission molecule TPE onto IAPP, allowing real-time monitoring of IAPP oligomer formation and potential application in the diagnosis of T2D.
BIOPHYSICAL CHEMISTRY
(2024)
Review
Biochemistry & Molecular Biology
Ajit Kumar Bishoyi, Pratiksha H. Roham, Kavitha Rachineni, Shreyada Save, M. Asrafuddoza Hazari, Shilpy Sharma, Ashutosh Kumar
Summary: The overexpression of hIAPP in T2DM is associated with misfolding of the peptide, formation of amyloid deposits, and death and dysfunction of pancreatic beta-islets. Studies have shown that during aggregation, hIAPP undergoes conformational changes from helix to beta-sheet and finally to left-handed helical aggregates, with intermediates causing cellular toxicity.
BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Jinming Wu, Xiaoying Yin, Huixian Ye, Zhonghong Gao, Hailing Li
Summary: Metalloporphyrins show potential as therapeutic agents for type 2 diabetes, with anionic metalloporphyrins such as FeTBAP and MnTBAP being effective inhibitors against hIAPP fibrillation. Iron center porphyrins are more effective than manganese center porphyrins in inhibiting hIAPP fibrillation.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Endocrinology & Metabolism
Joseph J. Castillo, Alfred C. Aplin, Daryl J. Hackney, Meghan F. Hogan, Nathalie Esser, Andrew T. Templin, Rehana Akter, Steven E. Kahn, Daniel P. Raleigh, Sakeneh Zraika, Rebecca L. Hull
Summary: The study found that aggregation of IAPP is toxic to islet endothelial cells and induces inflammatory responses, resulting in decreased capillary density, increased capillary diameter, and an increased number of pericytes.
Article
Biochemistry & Molecular Biology
Jufei Xu, Ting Zheng, Xiangyi Huang, Yanan Wang, Guowei Yin, Weihong Du
Summary: This study investigated the inhibition of procyanidine on hIAPP and A beta aggregation through diverse biophysical and biochemical methods. Procyanidine effectively inhibited the aggregation of both peptides through hydrophobic and hydrogen bonding interactions, dissolved aged fibrils into nanoscale particles, and ameliorated cytotoxicity and membrane leakage. The compound showed better binding affinity and inhibitory effects on hIAPP, suggesting its potential as a prospective inhibitor against hIAPP, offering a possible strategy for T2DM and AD treatments.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Cell Biology
Carine Marmentini, Renato C. S. Branco, Antonio C. Boschero, Mirian A. Kurauti
Summary: Islet amyloid polypeptide is a hormone co-secreted with insulin by pancreatic beta-cells and is found in patients with type 2 diabetes. Investigating aspects related to amyloid formation is crucial for developing strategies towards beta-cell protection. Approaches to prevent islet amyloid cytotoxicity have shown promise in improving beta-cell function and preventing hyperglycemia.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Adam El Saghir, Gianluca Farrugia, Neville Vassallo
Summary: hIAPP is a peptide hormone associated with protein misfolding disorders, impacting soluble amyloid deposition in the pancreas and brain through interaction with biological membranes. Future research should involve more physiologically-relevant studies for a better understanding of in vivo interactions, and there is an urgent need for developing effective therapeutic strategies to inhibit hIAPP-phospholipid interactions.
CHEMISTRY AND PHYSICS OF LIPIDS
(2021)