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Expression of BC1 Impairs Spatial Learning and Memory in Alzheimer’s Disease Via APP Translation

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Abstract

Aggregation of amyloid-β (Aβ) peptides, which are the cleavage products of amyloid precursor protein (APP), is a major pathological hallmark in the brain of Alzheimer’s disease (AD). Now, we know little about the roles of APP translation in the disease progression of AD. Here, we show that BC1, a long noncoding RNA (lncRNA), is expressed in the brain of AD mice. BC1 induces APP mRNA translation via association with a fragile X syndrome protein (FMRP). Inhibition of BC1 or BC1-FMRP association in AD mice blocks aggregation of Aβ in the brain and protects against the spatial learning and memory deficits. Expression of exogenous BC1 in excitatory pyramidal neurons of mice induces Aβ peptides accumulation and the spatial learning and memory impairments. This study provides a novel mechanism underlying aggregation of Aβ peptides via BC1 induction of APP mRNA translation and hence warrants a promising target for AD therapy.

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Abbreviations

Aβ:

Amyloid-β

APP:

Amyloid precursor protein

FMRP:

Fragile X syndrome protein

LTP:

Long-term potentiation

lncRNA:

Long noncoding RNA

LNA:

Locked-nucleic acid-modified

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Acknowledgments

We greatly thank Dr. Anbing Shi (Department of Biochemistry, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China) for the comments on manuscript. This work was supported by National Natural Science Foundation of China (grant number: 91632306 YL; 51627807 YL; 31721002 Y.L.; 31571039 LQZ; 81771150 LQZ; 91632114 LQZ). Top-Notch Young Talents Program of China of 2014 and Academic Frontier Youth Team of Huazhong University of Science and Technology to Dr. Ling-Qiang Zhu.

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  1. Tongmei Zhang, Pei Pang and Zemin Fang contributed equally to this work.

Authors and Affiliations

  1. Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Tongmei Zhang, Pei Pang, Yu Guo, Hao Li, Xinyan Li, Tian Tian, Xin Yang, Wenting Chen, Shu Shu, Na Tang, Jianhua Wu, Houze Zhu & Youming Lu

  2. The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, 430030, China

    Tongmei Zhang, Pei Pang, Yu Guo, Hao Li, Xinyan Li, Tian Tian, Xin Yang, Wenting Chen, Shu Shu, Na Tang, Jianhua Wu, Houze Zhu, Lei Pei, Dan Liu, Qing Tian, Jian Wang, Lin Wang, Ling-Qiang Zhu & Youming Lu

  3. Department of Cardiothoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Zemin Fang

  4. Department of Neurobiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Lei Pei

  5. Department of Genetics, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 4030030, China

    Dan Liu

  6. Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Qing Tian & Ling-Qiang Zhu

  7. Research Center for Tissue Engineering and Regenerative Medicine, Department of Clinical Laboratory, The Union Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China

    Jian Wang & Lin Wang

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  1. Tongmei Zhang
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Zhang, T., Pang, P., Fang, Z. et al. Expression of BC1 Impairs Spatial Learning and Memory in Alzheimer’s Disease Via APP Translation. Mol Neurobiol 55, 6007–6020 (2018). https://doi.org/10.1007/s12035-017-0820-z

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