1دانشکده علوم زیستی، دانشگاه تحصیلات تکمیلی علوم پایه زنجان، زنجان، ایران
2دانشکده علوم زیستی، دانشگاه تحصیلات تکمیلی علوم پایه زنجان، جاده گاوازنگ، زنجان، ایران
3گروه زیست شناسی، واحد رودهن، دانشگاه آزاد اسلامی، رودهن، ایران
چکیده
در بین روشهای درمانی مورد استفاده برای بیماریهای مرتبط با تجمعات آمیلوئیدی، روشهای مبتنی بر استفاده از ترکیبات طبیعی با خاصیت آنتی آمیلوئیدوژنیک بسیار مورد توجه قرار گرفته است. اگرچه مطالعات in vitro و in vivo زیادی دلالت بر توانایی مهار فیبریلاسیون توسط این ترکیبات دارد ولی مکانیسم عمل این ترکیبات با یکدیگر متفاوت میباشد. در این مطالعه، با استفاده از رنج وسیعی از تکنیکها شامل فلورسانس تیوفلاوین T و نایل رد، جذب قرمز کنگو، و میکروسکوپ نیروی اتمی توانایی ملکول طبیعی تاکسیفولین در مهار فرایند فیبریلاسیون پروتئین لیزوزیم سفیده ی تخم مرغ مورد بررسی قرار گرفت. نتایج حاصل نشان داد که تاکسیفولین از طریق اتصال به تجمعات پیش فیبریلی اثرات مهاری خود را اعمال می نماید. بعلاوه، اتصال تاکسیفولین باعث تغییر مسیر فیبریلاسیون به سمت ایجاد ساختارهای کروی زنجیره ای شکل بزرگ میشود که دارای محتوای صفحات بتا کم و سطوح آبگریز در دسترس اندک میگردد. همچنین سنجش میزان فلورسانس تیوفلاوین T نشان داد که توانایی اتصال تاکسیفولین به تجمعات پیش فیبریلی با رشد آنها و تشکیل تجمعات پروتوفیبریلی بزرگ در انتهای فاز رشد کاهش می یابد. به نظر میرسد که نتایج حاصل در طراحی مهارکننده های تجمع پروتئینی مرتبط با بیماریهای تحلیل برنده ی سیستم عصبی موثر باشد.
A study on the inhibitory effects of taxifolin on amyloid fibrillation of hen egg white lysozyme
نویسندگان [English]
Mohsen Mahdavimehr1؛ Ali Akbar Meratan2؛ Ali Asghar Bagheri3؛ Fariba Khosravinejad3
1Department of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Iran.
2Department of Biological Sciences, Institute of Advanced Studies in Basic Sciences (IASBS), Zanjan, Iran.
3Department of Biology, Islamic Azad University, Roudehen Branch,Roudehen,Iran
چکیده [English]
Among therapeutic approaches for amyloid-related diseases, attention has recently turned to the use of natural products as effective anti-aggregation compounds. Although a wealth of in vitro and in vivo evidence indicates some common inhibitory activity of these compounds, they don’t generally suggest the same mechanism of action. In the present study, using a range of techniques including Thioflavin T and Nile red fluorescence assays, Congo red absorbance measurements, and atomic force microscopy the ability of taxifolin on the inhibition of HEWL amyloid fibrillation was investigated. Obtained results demonstrated that taxifolin exerts its inhibitory effect by binding to HEWL prefibrillar species. Furthermore, it’s binding results in diverting the amyloid pathway toward formation of very large globular, chain-like aggregates with low β-sheet content and reduced solvent-exposed hydrophobic patches. ThT fluorescence measurements show that the binding capacity of taxifolin is significantly reduced, upon generation of large protofibrillar aggregates at the end of growth phase. We believe these results may help design promising inhibitors of protein aggregation for amyloid-related diseases.
کلیدواژه‌ها [English]
amyloid, Atomic Force Microscopy, Protein Aggregation, Taxifolin
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