Lithium ức chế sự thay đổi phosphoryl hóa tau do stress ở hồi hải mã chuột

Journal of Neural Transmission - Tập 113 - Trang 1803-1814 - 2006
S. Yoshida1,2, M. Maeda1, S. Kaku3, H. Ikeya4, K. Yamada2, S. Nakaike1
1Pharmacology Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co., LTD., Saitam, Japan
2Laboratory of Neuropsychopharmacology, Kanazawa University Graduate School of Natural Science & Technology, Kakuma-machi, Japan
3Medicinal Pharmacology Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co., LTD, Saitam, Japan
4Lead Generation Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co., LTD., Saitam, Japan

Tóm tắt

Đã có ý kiến cho rằng sự hyperphosphoryl hóa của protein tau liên kết với vi ống do stress có thể tham gia vào giai đoạn đầu của quá trình sinh bệnh Alzheimer. Trong nghiên cứu hiện tại, chúng tôi đã điều tra tác động của stress nước lạnh (CWS) lên phosphoryl hóa tau trong hồi hải mã chuột và tác động của chất ức chế GSK-3β, LiCl, lên sự thay đổi mức độ phosphoryl hóa tau do CWS gây ra thông qua phân tích immunoblot. Việc tiếp xúc với CWS đã làm tăng phosphoryl hóa tau tại các vị trí Tau-1 (Ser199/202), AT8 (Ser202/Thr205) và Ser396. Những thay đổi trong phosphoryl hóa tau do CWS gây ra tại các vị trí Ser199/202 và Ser396, nhưng không ở Ser202/Thr205, đã bị LiCl làm giảm đáng kể. Mức độ tau tổng thể cũng cho thấy xu hướng tăng rõ rệt sau CWS, xu hướng này cũng bị LiCl chống lại. Cuối cùng, chúng tôi đã chỉ ra rằng CWS làm tăng dạng hoạt động của GSK-3β đã phosphoryl hóa tại Tyr216. Những kết quả này gợi ý rằng sự gia tăng tau phosphoryl hóa do CWS gây ra trong hồi hải mã một phần là do sự kích hoạt của GSK-3β.

Từ khóa

#tau protein #hồi hải mã #phosphoryl hóa #ôxy hóa stress #GSK-3β #LiCl #bệnh Alzheimer

Tài liệu tham khảo

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