Toward understanding the role of genomic repeat elements in neurodegenerative diseases  

作　　者：Zhengyu An Aidi Jiang Jingqi Chen 

机构地区：[1]Institute of Science and Technology for Brain-Inspired Intelligence,Fudan University,Shanghai,China [2]MOE Frontiers Center for Brain Science,Fudan University,Shanghai,China [3]MOE Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence,Fudan University,Shanghai,China [4]Zhangjiang Fudan International Innovation Center,Shanghai,China

出　　处：《Neural Regeneration Research》2025年第3期646-659,共14页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China, No.61932008;Natural Science Foundation of Shanghai, No.21ZR1403200 (both to JC)。

摘　　要：Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.

关 键 词：Alzheimer's disease ATAXIA deep learning long-read sequencing NEURODEGENERATION neurodegenerative diseases Parkinson's disease repeat element structural variant 

分 类 号：R741[医药卫生—神经病学与精神病学]