Anti-fibrillogenic and fibril destabilizing effects of metal ions on cystatin fibrils |
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| Institution: | 1. Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, UP, India;2. Department of Chemistry, Faculty of Science, Aligarh Muslim University, Aligarh 202002, UP, India;3. Department of Biochemistry, Sheri Kashmir Institute of Medical Sciences, Srinagar 190011, JK, India;1. Centre for Environmental Management of Degraded Ecosystems, University of Delhi, Delhi 110007, India;2. Malaria Research Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Marg, New Delhi 110067, India;1. Division of Cardiology and Cardiovascular Surgery, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;2. Serviço de Hemodinâmica, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Belo Horizonte, Minas Gerais, Brazil;3. Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;4. Serviço de Hemodinâmica, Hospital Santa Helena, Cabo Frio, Rio de Janeiro, Brazil;5. Harrington Heart and Vascular Institute, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, Ohio;1. Molecular Genetics Laboratory, Department of Biotechnology & Bioinformatics, North-Eastern Hill University, Shillong, Meghalaya-793022, India;2. Department of Biochemistry, Indian Institute of Science, Bangalore, 560 012, India;1. University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;2. University of South Florida College of Medicine, Tampa, FL, USA;3. Medical University of South Carolina, Charleston, SC, USA;4. Paparella Ear Head & Neck Institute, USA;5. Wayne State University, Detroit, MI, USA;6. Medical College Wisconsin, Milwaukee, WI, USA |
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| Abstract: | Metals such as Cu2+, Fe3+, and Zn2+ are major contributors to the biology of a brain in stages of health, aging, and disease because of their unique effects on both protein structures (misfolding) and oxidative stress. The relationship between metal ions and neurodegenerative diseases is very complicated. Our study highlights how metal ions influence amyloid formation at low pH and on preformed amyloid fibrils. By using thioflavin T assay, ANS fluorescence, Congo red assay, circular dichroism, and microscopy to elucidate the effects of Cu2+, Fe3+, and Zn2+ on goat brain cystatin (GBC) aggregation at low pH. Results showed that Cu2+ and Fe3+ inhibit fibril formation of GBC by promoting amorphous aggregates. However, Zn2+ exclusively promotes fibril formation at low pH, leading to the formation of more ordered aggregates. Furthermore, the combined results of these complementary methods also suggested that Cu2+ and Fe3+ destabilize the β-sheet secondary structure of preformed amyloid fibrils of GBC. |
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| Keywords: | Goat brain cystatin Metal ions Fibrillation Amyloidosis Low pH |
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