Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Axit Retinoic Toàn Truyền Hiệu Ứng Lợi Ích Bảo Vệ Thần Kinh Trong Bệnh Tê Liệt Tủy Giống Như Tg (SOD1*G93A)1Gur Mice
Tóm tắt
Axit retinoic toàn truyền (ATRA), một ligand của thụ thể axit retinoic, có thể điều chỉnh nhiều quá trình sinh học bằng cách kích hoạt các tín hiệu axit retinoic. Các nghiên cứu gần đây đã chỉ ra rằng ATRA có nhiều tác dụng bảo vệ thần kinh và do đó làm giảm sự tiến triển của bệnh trong nhiều bệnh thần kinh khác nhau. Các nghiên cứu trước đây của chúng tôi phát hiện rằng tín hiệu axit retinoic bị suy giảm đã làm giảm ALDH1A2, một synthetase thiết yếu của ATRA, trong tủy sống của chuột ALS. Ở đây, chúng tôi đã đánh giá tác dụng bảo vệ và phục hồi thần kinh của ATRA trong mô hình chuột chuyển gen SOD1-G93A mắc bệnh ALS. Chúng tôi đã cho ATRA (3 mg/kg) hàng ngày từ giai đoạn khởi đầu đến giai đoạn tiến triển trong 5 tuần. Các kiểm tra hành vi cho thấy ATRA đã cải thiện sức mạnh cầm nắm của các chi trước ở chuột ALS và có thể làm chậm sự tiến triển của bệnh, nhưng không làm thay đổi trọng lượng cơ thể. ATRA có thể hoàn toàn đảo ngược tín hiệu thụ thể axit retinoic alpha (RARα) bị suy giảm trong tủy sống của chuột ALS. Hiệu ứng này đi kèm với việc tăng cường sự phân hủy các protein bị gập sai thông qua hệ thống ubiquitin-proteasome, điều chỉnh căng thẳng oxy hóa, ức chế sự kích hoạt tế bào thần kinh đệm và thúc đẩy sự phục hồi tín hiệu thần kinh dinh dưỡng. Các phát hiện của chúng tôi là lần đầu tiên chỉ ra rằng tín hiệu axit retinoic bị tổn hại liên quan đến bệnh sinh của ALS, và ATRA có thể tạo ra bảo vệ thần kinh chức năng thông qua sửa chữa tín hiệu axit retinoic bị hư hại.
Từ khóa
#Axit retinoic toàn truyền #bảo vệ thần kinh #bệnh tê liệt tủy #chuột chuyển gen #tín hiệu axit retinoicTài liệu tham khảo
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