Affiliation:
1. Department of Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Tokyo 162-8601, Japan
Abstract
Alzheimer’s disease causes the destruction of cranial nerve cells and is said to be caused by neuronal cell death due to the accumulation of amyloid-β protein. One method for the treatment of Alzheimer’s disease is to reduce the toxicity of the amyloid beta protein. Among the possibilities is to reduce toxicity by changing the secondary structure of the protein. In this study, the secondary structure of the protein was verified by binding a zinc complex to the protein and irradiating it with an infrared free-electron laser (IR-FEL). By binding Salen-Type zinc complexes to human serum albumin (HSA) and irradiating it with IR-FEL, structural changes were observed in the α-helix and β-sheet, the secondary structure of HSA. In addition to researching the possibility of binding zinc complexes to small proteins, docking simulations were examined. GOLD docking simulations showed that it is possible to bind zinc complexes to lysozyme (Lyz), a small protein. These results suggest that binding zinc complexes to amyloid-β and inducing a secondary conformational change through IR-FEL irradiation could be used for the treatment of Alzheimer’s disease by making the complexes lose their toxicity.
Reference78 articles.
1. Pathogenesis and prevention of dementia;Sagai;Jpn. Hum. Care Sci. J.,2010
2. γ-secretase for the treatment of Alzheimer’s disease Structure-Activity Relationships;Clin. Neurol.,2008
3. De Benedictis, C.A., Vilella, A., and Grabrucker, A.M. (2019). The Role of Trace Metals in Alzheimer’s Disease, Codon Publications.
4. Crosstalk of copper and zinc in the pathogenesis of vascular dementia;Kawahara;J. Clin. Biochem. Nutr.,2022
5. Molecular-Level Examination of Cu2+ Binding Structure for Amyloid Fibrils of 40-Residue Alzheimer’s β by Solid-State NMR Spectroscopy;Parthasarathy;J. Am. Chem. Soc.,2011