Loại bỏ c-Jun N-terminal Kinase 1 bảo vệ chống lại các suy giảm nhận thức do chuyển hóa gây ra ở vùng hồi hải mã

Springer Science and Business Media LLC - Tập 97 - Trang 1723-1733 - 2019
Oriol Busquets1,2,3,4, Miren Ettcheto1,2,3,4, Àuria Eritja1, Triana Espinosa-Jiménez1,3,4, Ester Verdaguer3,4,5, Jordi Olloquequi6, Carlos Beas-Zarate7, Ruben Dario Castro-Torres3,4,5,7, Gemma Casadesús8, Carme Auladell3,4,5, Mònica Bulló9,10, Jaume Folch2,3, Antoni Camins1,3,4,6
1Departament de Farmacologia, Toxicologia i Química Terapèutica, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, Barcelona, Spain
2Departament de Bioquímica i Biotecnologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, Spain
3Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
4Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
5Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
6Laboratory of Cellular and Molecular Pathology, Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Talca, Chile
7Laboratorio de Regeneración y Desarrollo Neural, Departamento de Biología Celular y Molecular, Instituto de Neurobiología, CUCBA, Zapopan, Mexico
8Department of Biological Sciences, Kent State University, Kent, USA
9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain.
10CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain

Tóm tắt

Sự phát triển của những thay đổi chuyển hóa như kháng insulin đã được liên kết với sự rối loạn trong khả năng oxy hóa của ty thể, sự kích thích các phản ứng viêm thần kinh, và sự xuất hiện của các suy giảm nhận thức trong não. c-Jun N-terminal Kinase 1 (JNK1) được coi là một yếu tố điều hòa chính của những cơ chế này. Nghiên cứu hiện tại xác định hiệu ứng bảo vệ của việc loại bỏ JNK1 toàn thân trong điều kiện chế độ ăn nhiều chất béo (HFD). Cụ thể, dữ liệu cho thấy những con chuột thiếu JNK1 cho thấy sự nhạy cảm insulin và hoạt động ty thể tăng lên, cũng như giảm trọng lượng cơ thể, cùng với sự phản ứng của tế bào sao và vi khối u. Cuối cùng, những động vật này cũng được bảo vệ chống lại những suy giảm nhận thức do HFD gây ra như được đánh giá thông qua bài kiểm tra nhận dạng đối tượng mới, quan sát các gai nhánh, và các mức độ của BDNF hoặc các protein khác như spinophilin và ARC. Do đó, việc điều chỉnh hoạt động của JNK1 dường như là một cách tiếp cận đầy hứa hẹn cho việc thiết kế các liệu pháp nhằm điều trị các suy giảm nhận thức do chuyển hóa gây ra.

Từ khóa

#JNK1 #kháng insulin #suy giảm nhận thức #ty thể #phản ứng viêm thần kinh #BDNF #chế độ ăn nhiều chất béo

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