Expression of BC1 Impairs Spatial Learning and Memory in Alzheimer’s Disease Via APP Translation
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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The lncRNA BC1 can induce spatial learning and memory impairment by enhancing APP translation in AD mouse brain.
“The lncRNA BC1 can induce spatial learning and memory impairment by enhancing APP translation in AD mouse brain [617].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [617]
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Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
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- Authors
- Zhang, T., Pang, P., Fang, Z., Guo, Y., Li, H., Li, X., Tian, T., Yang, X., Chen, W., Shu, S., Tang, N., Wu, J., Zhu, H., Pei, L., Liu, D., Tian, Q., Wang, J., Wang, L., Zhu, L.-Q., & Lu, Y.
- Affiliations
- Huazhong University of Science and Technology (CN)
- Tongji Hospital (CN)
- Wuhan Union Hospital (CN)
- Corresponding author
- Liu, Dan
- Lu, Youming
- ORCID
- Venue
- Molecular Neurobiology
- Published
- 2017-11-13
- Volume
- 55
- Issue
- 7
- Pages
- 6007-6020
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W2768018325
- Cited by
- 52
- References
- 54
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 1 · 2023: 9 · 2022: 3 · 2021: 12 · 2020: 9 · 2019: 4 · 2018: 4 · 2017: 1
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (91632306, 51627807, 31571039, 91632114)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid-beta aggregation, amyloid precursor protein, FMRP, spatial learning and memory, AD mouse model, therapeutic target
- MeSH terms
- Alzheimer Disease, Animals, Memory, Memory Disorders, Mice, Inbred C57BL, Mice, Transgenic, RNA, Messenger, Protein Biosynthesis, Amyloid beta-Protein Precursor, Fragile X Messenger Ribonucleoprotein 1, RNA, Long Noncoding, Spatial Learning
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