Vai trò của Protein tiền thân Amyloid (APP) và các dẫn xuất của nó trong sinh học và xác định số phận tế bào của tế bào gốc thần kinh

Molecular Neurobiology - Tập 55 - Trang 7107-7117 - 2018
Raquel Coronel1, Adela Bernabeu-Zornoza1, Charlotte Palmer1, Mar Muñiz-Moreno2, Alberto Zambrano1, Eva Cano3, Isabel Liste1
1Unidad de Regeneración Neural, Unidad Funcional de Investigación de Enfermedades Crónicas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
2Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC); CNRS-UMR7104; INSERM-U964, Université de Strasbourg, Illkirch, France
3Unidad de Neuroinflamación. Unidad Funcional de Investigación de Enfermedades Crónicas, Instituto de Salud Carlos III (ISCIII), Madrid, Spain

Tóm tắt

Protein tiền thân amyloid (APP) là một thành viên của họ protein APP, và các quá trình enzym khác nhau dẫn đến việc sản xuất nhiều dẫn xuất thể hiện các chức năng sinh học khác nhau. APP có liên quan đến bệnh lý của bệnh Alzheimer (AD), rối loạn thoái hóa thần kinh phổ biến nhất gây ra chứng mất trí nhớ. Hơn nữa, người ta tin rằng những cá nhân bị hội chứng Down (DS) có sự biểu hiện APP gia tăng, do một bản sao bổ sung của nhiễm sắc thể 21 (Hsa21), chứa gen cho APP. Tuy nhiên, chức năng sinh lý của APP vẫn chưa được làm sáng tỏ. APP được biết đến là đóng vai trò quan trọng trong sự phát triển và trưởng thành của thần kinh trong quá trình phát triển não, có thể bằng cách ảnh hưởng đến sự phát triển, định hình số phận tế bào và tái tạo tế bào thần kinh của các tế bào gốc thần kinh (NSCs). Sự cắt peptide của APP diễn ra chủ yếu qua hai con đường loại trừ lẫn nhau: con đường không sinh amyloid hoặc con đường sinh amyloid. Các con đường thay thế khác (con đường η-secretase, δ-secretase và meprin) cũng đã được mô tả cho việc xử lý sinh lý của APP. Các chất chuyển hóa khác nhau được tạo ra từ các con đường này, bao gồm APPα hòa tan (sAPPα), APPβ hòa tan (sAPPβ), peptide β-amyloid (Aβ) và miền nội bào của APP (AICD), có các chức năng khác nhau được xác định bởi sự khác biệt cấu trúc, sự cân bằng và nồng độ liên quan đến các mảnh vụn khác từ APP. Bài tổng quan này thảo luận về những quan sát gần đây liên quan đến các chức năng có thể xảy ra của APP và các dẫn xuất proteolytic của nó trong sinh học và xác định kiểu hình của NSCs. Điều này có thể quan trọng cho việc hiểu rõ hơn về sinh bệnh học và phát triển các ứng dụng điều trị trong tương lai cho AD và/hoặc DS, các bệnh mà sự biến đổi trong tái tạo tế bào thần kinh đã được mô tả.

Từ khóa

#Protein tiền thân amyloid #APP #bệnh Alzheimer #hội chứng Down #tế bào gốc thần kinh #sinh lý học #dẫn xuất proteolytic

Tài liệu tham khảo

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