Lipids uniquely alter rates of insulin aggregation and lower toxicity of amyloid aggregates |
| |
| Institution: | 1. Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, United States;2. Department of Biotechnology, Binh Duong University, Thu Dau Mot 820000, Viet Nam;3. Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, United States;1. ECOMARE – Laboratory for Innovation and Sustainability of Marine Biological Resources, CESAM – Centre for Environmental and Marine Studies, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal;2. Mass Spectrometry Centre & LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal;3. ECOMARE - Laboratory for Innovation and Sustainability of Marine Biological Resources, CESAM – Centre for Environmental and Marine Studies, Department of Biology, Campus Universitário de Santiago, University of Aveiro, 3810-193 Aveiro, Portugal;4. GreenCoLab – Associação Oceano Verde, University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal;5. Department of Economics and Business, Universitat Pompeu Fabra, Barcelona School of Management, Barcelona, Spain;1. Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Palle Juel-Jensens Boulevard 99, 8200 Aarhus, Denmark;2. School of Pharmacy, Liverpool John Moore University, Byrom Street, Liverpool L3 3AF, United Kingdom;1. Graduate School of Technology, Industrial and Social Sciences, Tokushima University, Tokushima 770-8502, Japan;2. Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8505, Japan;3. Diabetic Neuropathy Project, Department of Diseases and Infection, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan;1. Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy;2. Department of Translational and Precision Medicine, Sapienza, University of Rome, Rome, Italy;3. Maria Cecilia Hospital, Cotignola, RA, Italy |
| |
| Abstract: | Amyloid formation is a hallmark of many medical diseases including diabetes type 2, Alzheimer's and Parkinson diseases. Under these pathological conditions, misfolded proteins self-assemble forming oligomers and fibrils, structurally heterogeneous aggregates that exhibit a large variety of shapes and forms. A growing body of evidence points to drastic changes in the lipid profile in organs affected by amyloidogenic diseases. In this study, we investigated the extent to which individual phospho- and sphingolipids, as well as their mixtures can impact insulin aggregation. Our results show that lipids and their mixtures uniquely alter rates of insulin aggregation simultaneously changing the secondary structure of protein aggregates that are grown in their presence. These structurally different protein-lipid aggregates impact cell viability to different extent while using distinct mechanisms of toxicity. These findings suggest that irreversible changes in lipid profiles of organs may trigger formation of toxic protein species that in turn are responsible for the onset and progression of amyloidogenic diseases. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
