Một đánh giá về bằng chứng cho con đường Wnt kinh điển trong rối loạn phổ tự kỷ

Molecular Autism - Tập 3 - Trang 1-12 - 2012
Hans Otto Kalkman1
1Neuroscience Department, Novartis Institute of Biomedical Research, Basel, Switzerland

Tóm tắt

Các biến thể số lượng bản sao của microdeletion và microduplication được phát hiện ở bệnh nhân rối loạn phổ tự kỷ, và trong một số trường hợp, chúng bao gồm các gen có liên quan đến con đường tín hiệu Wnt kinh điển (ví dụ, FZD9, BCL9 hoặc CDH8). Các nghiên cứu liên kết điều tra WNT2, DISC1, MET, DOCK4 hoặc AHI1 cũng cung cấp bằng chứng rằng con đường Wnt kinh điển có thể bị ảnh hưởng trong tự kỷ. Việc sử dụng thuốc trong thai kỳ với natri valproate hoặc thuốc chống trầm cảm làm tăng nguy cơ tự kỷ. Trong các nghiên cứu trên động vật, đã phát hiện rằng các loại thuốc này thúc đẩy tín hiệu Wnt, bao gồm, trong số những thứ khác, sự gia tăng biểu hiện gen Wnt2. Đáng chú ý là, thông tin di truyền hiện có cho thấy rằng không chỉ sự kích hoạt con đường Wnt kinh điển, mà cả sự ức chế cũng dường như làm tăng nguy cơ tự kỷ. Con đường Wnt kinh điển đóng vai trò trong sự phát triển của nhánh thần kinh, và hoạt động kém tối ưu ảnh hưởng tiêu cực đến bộ nhánh thần kinh. Về nguyên tắc, điều này cung cấp một giải thích hợp lý về lý do tại sao cả hoạt động kém và hoạt động quá mức có thể tạo ra một tập hợp các triệu chứng hành vi và nhận thức tương tự. Tuy nhiên, nếu không có một dấu hiệu sinh học được xác nhận để phân loại hoạt động của con đường Wnt kinh điển, việc điều trị bệnh nhân bằng các hợp chất có thể làm thay đổi hoạt động của con đường có lẽ là quá nguy hiểm.

Từ khóa

#rối loạn phổ tự kỷ #con đường Wnt kinh điển #gen #thuốc chống trầm cảm #hoạt động tín hiệu Wnt

Tài liệu tham khảo

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