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Yếu tố NGF và FGF2 tiết ra từ C6 Glioma điều chỉnh quá trình xử lý APP thần kinh thông qua sự tăng biểu hiện ADAM10 và giảm biểu hiện BACE1, tương ứng
Tóm tắt
Sự tích tụ quá mức của amyloid-β (Aβ) do sự cắt đứt protein tiền thân amyloid (APP) được cho là nguyên nhân chính gây ra bệnh Alzheimer (AD). Hai enzym chính ADAM10 và BACE1 tham gia vào quá trình cắt đứt đầu tiên của APP, dẫn đến sự khởi động của hai con đường, con đường amyloidogenic và con đường không amyloidogenic, tương ứng. Việc thay đổi chuyển hóa APP theo hướng con đường không amyloidogenic được cho là làm giảm sản xuất Aβ. Các nghiên cứu đã chỉ ra rằng, in vivo, các yếu tố thần kinh ngoại sinh khiến APP dễ dàng đi vào con đường không amyloidogenic. Vì các tế bào hình sao tiết ra một loạt các yếu tố thần kinh, chúng tôi đã nghiên cứu vai trò của các yếu tố do tế bào hình sao tạo ra trong động lực sản xuất Aβ ở các tế bào thần kinh. Kết quả cho thấy rằng dịch nuôi cấy tế bào u nguyên bào thần kinh C6 (GCM), thu được từ các tế bào u nguyên bào thần kinh C6 được nuôi cấy, ức chế sản xuất Aβ1-42 và chuyển hướng xử lý APP về con đường không amyloidogenic trong các tế bào APPswe-HEK293. Hiệu ứng như vậy được quy cho hai enzym cắt APP chính, ADAM10 và BACE1. Hai yếu tố thần kinh trong GCM, yếu tố tăng trưởng thần kinh và yếu tố tăng trưởng nguyên bào sợi 2, chịu trách nhiệm cho sự tăng biểu hiện ADAM10 và giảm biểu hiện BACE1, tương ứng. Những phát hiện của chúng tôi nâng cao hiểu biết về mối quan hệ giữa tế bào hình sao và sự sản sinh Aβ, cho thấy rằng việc kích thích các yếu tố thần kinh tế bào hình sao có thể làm chậm quá trình tiến triển của AD.
Từ khóa
#Alzheimer #amyloid-β #APP #ADAM10 #BACE1 #yếu tố tăng trưởng thần kinh #yếu tố tăng trưởng nguyên bào sợiTài liệu tham khảo
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