Article
Biochemistry & Molecular Biology
Giovanna Lucia Delogu, Benedetta Era, Sonia Floris, Rosaria Medda, Valeria Sogos, Francesca Pintus, Gianluca Gatto, Amit Kumar, Gunilla Torstensdotter Westermark, Antonella Fais
Summary: The study found that hydroxylated 2-phenylbenzofurans compounds exhibited strong inhibitory activity against alpha-glucosidase, with compound 16 showing the best performance. It also effectively inhibited IAPP aggregation without significant cytotoxicity.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
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
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
Chemistry, Analytical
Pin -Han Lin, Chang-Shun Tsai, Chia-Chien Hsu, I-Ren Lee, Yu-Xin Shen, Hsiu-Fang Fan, Yun-Wen Chen, Ling-Hsie Tu, Wei-Min Liu
Summary: The deposits of human islet amyloid polypeptide (IAPP) in the pancreas play a role in pancreatic β-cell dysfunction and are a common pathological hallmark of type II diabetes mellitus (T2DM). The study introduces a new near-infrared (NIR) fluorescent probe, AmySP-4-Nap-Ene, which can selectively bind to IAPP aggregates and differentiate between fibrillar and non-fibrillar forms. The probe shows potential for monitoring the accumulation of IAPP and imaging fibrils in vitro and in living cells.
Article
Neurosciences
Ying-Ying Yang, Yan-Tao Ren, Meng -Yu Jia, Chen-Yang Bai, Xiu-Ting Liang, Hui-Ling Gao, Man-Li Zhong, Tao Wang, Chuang Guo
Summary: Recent evidence suggests that human islet amyloid polypeptide (h-IAPP) may interact with A β or tau in Alzheimer's disease (AD) and have a potential therapeutic effect on neurodegenerative disorders with tauopathy, such as AD. Long-term h-IAPP treatment attenuated tau hyperphosphorylation levels, induced neuroinflammation and oxidative damage, prevented synaptic loss and neuronal degeneration, and alleviated behavioral deficits in a mouse model of tauopathy.
EXPERIMENTAL NEUROLOGY
(2023)
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)
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
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.
Review
Cell Biology
Angelina S. Bortoletto, Ronald J. Parchem
Summary: Patients with type 2 diabetes mellitus have a significantly higher risk of developing dementia, possibly due to increased secretion of amylin. This review summarizes the mechanisms by which amylin accumulation may cause neuronal damage and discusses the importance of investigating new therapeutic targets for treating dementia.
NEURAL REGENERATION RESEARCH
(2023)
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
Medicine, Research & Experimental
Luiz E. M. Cardoso, Thatiany Souza Marinho, Fabiane Ferreira Martins, Marcia Barbosa Aguila, Carlos A. Mandarim-de-Lacerda
Summary: In this study, the effects of a glucagon-like peptide type 1 receptor agonist, semaglutide, on the turnover of islet extracellular matrix (ECM) components in an obese mouse model were investigated. The results showed that semaglutide improved the turnover of ECM components and reduced the formation of amyloid deposits.
Article
Endocrinology & Metabolism
Austin J. Taylor, Evgeniy Panzhinskiy, Paul C. Orban, Francis C. Lynn, David F. Schaeffer, James D. Johnson, Janel L. Kopp, C. Bruce Verchere
Summary: Loss of IAPP signaling may not increase the risk of pancreatic cancer in individuals with diabetes.
MOLECULAR METABOLISM
(2022)
Article
Clinical Neurology
Sylwia Libard, Irina Alafuzoff
Summary: This study aimed to investigate the association between pancreatic islet amyloid polypeptide (IAPP) and Alzheimer's disease neuropathological change (ADNC). Immunohistochemical (IHC) analyses were conducted on brain biopsies from subjects with idiopathic normal pressure hydrocephalus (iNPH) and post-mortem (PM) brain samples from aged individuals. The results showed that there was no specific expression of IAPP in human brain tissue, indicating that the association between IAPP and ADNC cannot be assessed.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ivan Alic, Pollyanna A. Goh, Aoife Murray, Erik Portelius, Eleni Gkanatsiou, Gillian Gough, Kin Y. Mok, David Koschut, Reinhard Brunmeir, Yee Jie Yeap, Niamh L. O'Brien, Jurgen Groet, Xiaowei Shao, Steven Havlicek, N. Ray Dunn, Hlin Kvartsberg, Gunnar Brinkmalm, Rosalyn Hithersay, Carla Startin, Sarah Hamburg, Margaret Phillips, Konstantin Pervushin, Mark Turmaine, David Wallon, Anne Rovelet-Lecrux, Hilkka Soininen, Emanuela Volpi, Joanne E. Martin, Jia Nee Foo, David L. Becker, Agueda Rostagno, Jorge Ghiso, Zeljka Krsnik, Goran Simic, Ivica Kostovi, Dinko Mitrecic, Paul T. Francis, Kaj Blennow, Andre Strydom, John Hardy, Henrik Zetterberg, Dean Nizetic
Summary: Research has shown that individuals with Down Syndrome exhibit Alzheimer's disease-like pathological changes, which can be successfully replicated in vitro cerebral organoids models. These findings suggest that DS cerebral organoids could serve as a potential detector for pre-morbid AD-risk populations, as well as a system for hypothesis-free drug screening and identification of natural suppressor genes for neurodegenerative diseases.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Ingrid C. Rulifson, Patrick Collins, Li Miao, Dana Nojima, Ki Jeong Lee, Miki Hardy, Jamila Gupte, Kelly Hensley, Kim Samayoa, Cynthia Cam, James B. Rottman, Mike Ollmann, William G. Richards, Yang Li
JOURNAL OF BIOLOGICAL CHEMISTRY
(2017)
Article
Endocrinology & Metabolism
Shanaka Stanislaus, Randy Hecht, Junming Yie, Todd Hager, Michael Hall, Chris Spahr, Wei Wang, Jennifer Weiszmann, Yang Li, Liying Deng, Dwight Winters, Stephen Smith, Lei Zhou, Yuesheng Li, Murielle M. Veniant, Jing Xu
Article
Biochemistry & Molecular Biology
Sally Yu Shi, Ya-Wen Lu, Zhi Liu, Jennitte Stevens, Christopher M. Murawsky, Vicki Wilson, Zhonghua Hu, William G. Richards, Mark Leo Michaels, Jun Zhang, Wei Yan, Yang Li
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Multidisciplinary Sciences
Sally Yu Shi, Ya-Wen Lu, Jason Richardson, Xiaoshan Min, Jennifer Weiszmann, William G. Richards, Zhulun Wang, Zhongqi Zhang, Jun Zhang, Yang Li
SCIENTIFIC REPORTS
(2018)
Article
Biochemistry & Molecular Biology
Xiaoshan Min, Jennifer Weiszmann, Sheree Johnstone, Wei Wang, Xinchao Yu, William Romanow, Stephen Thibault, Yang Li, Zhulun Wang
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Multidisciplinary Sciences
Zhengjian Zhang, Caroline Broderick, Marni Nishimoto, Teppei Yamaguchi, Sung-Jin Lee, Haili Zhang, Hui Chen, Mehaben Patel, Jay Ye, Alberto Ponce, Jennifer Brady, Helene Baribault, Yang Li, Wen-Chen Yeh
SCIENTIFIC REPORTS
(2020)
Article
Multidisciplinary Sciences
Tristan W. Fowler, Troy L. Mitchell, Claudia Y. Janda, Liqin Xie, Shengjiang Tu, Hui Chen, Haili Zhang, Jingjing Ye, Brian Ouyang, Tom Z. Yuan, Sung-Jin Lee, Maureen Newman, Nikita Tripuraneni, Erica S. Rego, Devin Mutha, Archana Dilip, Meghah Vuppalapaty, Helene Baribault, Wen-Chen Yeh, Yang Li
Summary: The study introduces a novel antibody-based platform for generating potent Wnt mimetics to address conditions like osteoporosis. The synthetic Wnt agonists demonstrate rapid bone building effects in murine models, indicating potential for therapeutic use in bone-related disorders.
NATURE COMMUNICATIONS
(2021)
Article
Gastroenterology & Hepatology
Liqin Xie, Russell B. Fletcher, Diksha Bhatia, Darshini Shah, Jacqueline Phipps, Shalaka Deshmukh, Haili Zhang, Jingjing Ye, Sungjin Lee, Lucas Le, Maureen Newman, Hui Chen, Asmiti Sura, Suhani Gupta, Laura E. Sanman, Fan Yang, Weixu Meng, Helene Baribault, Geertrui F. Vanhove, Wen -Chen Yeh, Yang Li, Chenggang Lu
Summary: The study demonstrates that modulation of Wnt signaling is a potential approach to treating epithelial damage in inflammatory bowel disease. Exogenous R-spondin and Wnt mimetics can repair damaged intestinal epithelium, reduce disease activity and inflammation. Among them, the Wnt mimetic SZN-1326-p, specific to receptors FZD5/8 and LRP6, shows robust repair effects.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Ophthalmology
Huy Nguyen, Hui Chen, Meghah Vuppalapaty, Elizabeth Whisler, Kelsey Ronarda Logas, Parthasarathy Sampathkumar, Russell Byron Fletcher, Asmiti Sura, Nicholas Suen, Suhani Gupta, Tom Lopez, Jay Ye, Shengjiang Tu, Menaka Bolaki, Wen-Chen Yeh, Yang Li, Sung-Jin Lee
Summary: This study developed a Norrin mimetic targeting FZD4 and LRP5, named SZN-413-p, and demonstrated its ability to promote the regeneration of functional blood vessels in animal models. After humanization, SZN-413 showed significant efficacy in reducing neovascularization and avascular areas in a mouse model. Moreover, it effectively reduced retinal vascular leakage in a rabbit model. These findings suggest that SZN-413 can offer a new therapeutic strategy for diabetic retinopathy.
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Huy Nguyen, Sung-Jin Lee, Yang Li
Summary: Retinal ischemia is a major cause of visual impairment and blindness worldwide, often associated with various disorders. Diabetic retinopathy is a common cause, and its exact pathogenesis remains unclear, but vascular leakage plays a significant role in visual impairment. Current treatments have limitations, therefore there is a need for new therapies to address vessel regeneration and reperfusion in ischemic retinal areas. The Wnt signaling pathway in the retina could provide a novel disease modifying therapy.
Article
Multidisciplinary Sciences
Jie Ding, Sung-Jin Lee, Lukas Vlahos, Kanako Yuki, Cara C. Rada, Vincent van Unen, Meghah Vuppalapaty, Hui Chen, Asmiti Sura, Aaron K. McCormick, Madeline Tomaske, Samira Alwahabi, Huy Nguyen, William Nowatzke, Lily Kim, Lisa Kelly, Douglas Vollrath, Andrea Califano, Wen-Chen Yeh, Yang Li, Calvin J. Kuo
Summary: Derangements of the blood-brain barrier (BBB) or blood-retinal barrier (BRB) occur in various disorders. A non-lipidated, FZD(4)-specific surrogate called L6-F4-2 has been developed and shown to improve BBB and BRB function. It also demonstrates systemic efficacy during ischemic stroke BBB dysfunction.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Hui Chen, Chenggang Lu, Sung-Jin Lee, Yang Li
Article
Biochemistry & Molecular Biology
Hui Chen, Chenggang Lu, Brian Ouyang, Haili Zhang, Zhong Huang, Diksha Bhatia, Sung-Jin Lee, Darshini Shah, Asmiti Sura, Wen-Chen Yeh, Yang Li
CELL CHEMICAL BIOLOGY
(2020)
Article
Biology
Maia Azubel, Stephen D. Carter, Jennifer Weiszmann, Jun Zhang, Grant J. Jensen, Yang Li, Roger D. Kornberg
Article
Biochemistry & Molecular Biology
Ognjen Grujic, Jennitte Stevens, Robert Y. -T. Chou, Jennifer V. Weiszmann, Laura Sekirov, Christy Thomson, Anita Badh, Stephanie Grauer, Brian Chan, Kevin Graham, Kathy Manchulenko, Thomas M. Dillon, Yang Li, Ian N. Foltz
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2017)