Integrated multi-omics analysis identifies potential therapeutic targets for Alzheimer’s diseaseOA
Because the pathogenesis of Alzheimer’s disease is multifactorial and complex,integrated multi-level omics analysis is essential to comprehensively elucidate its molecular alterations.We therefore utilized the well-established amyloid precursor protein/presenilin 1 mouse model to carry out an integrated multi-omics study using transcriptomic,proteomic,N^(6)-methyladenosine epitranscriptomic,and phosphoproteomic analyses.The results revealed substantial molecular alterations across multiple biological dimensions and the alteration in the expression of several key genes,such as GFAP,APP,and RTN4,in a mouse model of Alzheimer’s disease.The pronounced elevation of RTN4 in reactive astrocytes is indicative of its involvement in Alzheimer’s disease pathogenesis.Furthermore,we identified dysregulation of pathways related to endocytosis,highlighting the critical role of this process in disease progression.Our findings underscore the significant impact of post-transcriptional(N^(6)-methyladenosine methylation)and post-translational(phosphorylation)protein modifications,which have been underrepresented in Alzheimer’s disease research.The significant contribution made by this study is the integrated,multi-level omics analysis that we carried out to investigate the complex biological changes that occur in Alzheimer’s disease.Our findings provide novel insights into Alzheimer’s disease pathogenesis and suggest potential therapeutic targets,such as RTN4.
Hongli Li;Jin Kang;Zilin Liang;Xiaowei Wang;Lemei Zhu;Hanfen Tang;Weijun Peng
Department of Integrated Traditional Chinese&Western Medicine,The Second Xiangya Hospital,Central South University,Changsha,Hunan Province,ChinaDepartment of Rheumatology and Immunology,The Second Xiangya Hospital of Central South University,Changsha,Hunan Province,ChinaSchool of Integrated Chinese and Western Medicine,Hunan University of Chinese Medicine,Changsha,Hunan Province,ChinaDepartment of Pathology,The Second Xiangya Hospital,Central South University,Changsha,Hunan Province,ChinaDepartment of Integrated Traditional Chinese&Western Medicine,The Second Xiangya Hospital,Central South University,Changsha,Hunan Province,China Academician Workstation,Changsha Medical University,Changsha,Hunan Province,ChinaDepartment of Nutrition,Second Xiangya Hospital,Central South University,Changsha,Hunan Province,ChinaDepartment of Integrated Traditional Chinese&Western Medicine,The Second Xiangya Hospital,Central South University,Changsha,Hunan Province,China Academician Workstation,Changsha Medical University,Changsha,Hunan Province,China
医药卫生
amyloid-βamyloid precursor protein/presenilin 1astrocyteendocytosisglial fibrillary acidic proteinmulti-omicsnerve regenerationpost-transcriptional modificationpost-translational modificationRTN4
《Neural Regeneration Research》 2026 (8)
P.3769-3778,10
supported by the National Natural Science Foundation of China,No.82374552(to WP)the Natural Science Foundation of Hunan Province,Nos.2024JJ2086,2024JJ6597(to JK)the Science and Technology Innovation Program of Hunan Province,No.2022RC1220(to WP)Support Plan for High-Level Health and Medical Talents in Hunan Province,No.20240304076(to WP).
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