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Mol Neurobiol. 2018 Jul;55(7):6007-6020. doi: 10.1007/s12035-017-0820-z. Epub 2017 Nov 13.

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

Zhang T1,2, Pang P1,2, Fang Z3, Guo Y1,2, Li H1,2, Li X1,2, Tian T1,2, Yang X1,2, Chen W1,2, Shu S1,2, Tang N1,2, Wu J1,2, Zhu H1,2, Pei L2,4, Liu D5,6, Tian Q2,7, Wang J2,8, Wang L2,8, Zhu LQ2,7, Lu Y9,10.

Author information

1
Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
2
The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, 430030, China.
3
Department of Cardiothoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
4
Department of Neurobiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
5
The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, 430030, China. liudan_echo@hust.edu.cn.
6
Department of Genetics, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 4030030, China. liudan_echo@hust.edu.cn.
7
Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
8
Research Center for Tissue Engineering and Regenerative Medicine, Department of Clinical Laboratory, The Union Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.
9
Department of Physiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. lym@hust.edu.cn.
10
The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, 430030, China. lym@hust.edu.cn.

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.

KEYWORDS:

Alzheimer’s disease; Amyloid-β peptides; App; BC1; FMRP

PMID:
29134514
DOI:
10.1007/s12035-017-0820-z
[Indexed for MEDLINE]

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