Інгібування агрегації α-синуклеїну поліфенолами
DOI:
https://doi.org/10.15330/jpnubio.12.87-100Ключові слова:
α-синуклеїн, хвороба Паркінсона, амілоїдні фібрили, поліфеноли.Анотація
Хвороба Паркінсона (ХП) є другим за поширеністю нейродегенеративним захворюванням, що характеризується внутрішньоклітинними тілами Леві, які складаються переважно з амілоїдних фібрил, утворених α-синуклеїном (αSyn). Нативний αSyn є розчинним внутрішньо безладним білком, але при ХП він неправильно згортається в патологічну β-листову структуру, яка агрегується, порушує функцію мітохондрій, викликає запалення і, в кінцевому підсумку, призводить до загибелі нейронів. Оскільки агрегація αSyn відбувається шляхом багатоступеневого зародження та швидкого подовження фібрил, інгібування цього процесу, зокрема шляхом блокування росту фібрил на кінцях, є перспективною терапевтичною стратегією. Цей огляд зосереджується на поліфенолах як інгібіторах агрегації амілоїдних фібрил αSyn. Поліфеноли модулюють агрегацію за допомогою різних механізмів, включаючи стабілізацію мономерів, перенаправлення в нетоксичні олігомери поза шляхом (наприклад, EGCG, ресвератрол), руйнування існуючих фібрил (байкалеїн) та ковалентну модифікацію залишків лізину αSyn (кверцетин, гідрокситирозол). Важливо, що метаболіти харчових поліфенолів (такі як 3-HPPA), що походять з мікробіоти кишечника, можуть проникати через гематоенцефалічний бар'єр і сильно послаблювати зародження αSyn, що підкреслює їх терапевтичний потенціал при ПД.
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