TY - JOUR
T1 - Down-regulated expression of microRNA-338-5p contributes to neuropathology in Alzheimer's disease
AU - Qian, Qi
AU - Zhang, Jian
AU - He, Fang Ping
AU - Bao, Wang Xiao
AU - Zheng, Ting Ting
AU - Zhou, Dong Ming
AU - Pan, Hong Yu
AU - Zhang, Heng
AU - Zhang, Xiao Qin
AU - He, Xiao
AU - Sun, Bing Gui
AU - Luo, Ben Yan
AU - Chen, Chu
AU - Peng, Guo Ping
N1 - Publisher Copyright:
© FASEB
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Alzheimer's disease (AD) is a leading cause of dementia. However, the mechanisms responsible for development of AD, especially for the sporadic variant, are still not clear. In our previous study, we discovered that a small noncoding RNA (miR-188-3p) targeting β-site amyloid precursor protein cleaving enzyme (BACE)-l, a key enzyme responsible for Aβ formation, plays an important role in the development of neuropathology in AD. In the present study, we identified that miR-338-5p, a new miRNA that also targets BACE1, contributes to AD neuropathology. We observed that expression of miR-338-5p was significantly down-regulated in the hippocampus of patients with AD and 5XFAD transgenic (TG) mice, an animal model of AD. Overexpression of miR-338-5p in the hippocampus of TG mice reduced BACE1 expression, Aβ formation, and neuroinflammation. Overexpression of miR-338-5p functionally prevented impairments in long-term synaptic plasticity, learning ability, and memory retention in TG mice. In addition, we provide evidence that down-regulated expression of miR-338-5p in AD is regulated through the NF-κB signaling pathway. Our results suggest that down-regulated expression of miR-338-5p plays an important role in the development of AD.—Qian, Q., Zhang, J., He, F.-P., Bao, W.-X., Zheng, T.-T., Zhou, D.-M., Pan, H.-Y., Zhang, H., Zhang, X.-Q., He, X., Sun, B.-G., Luo, B.-Y., Chen, C., Peng, G.-P. Down-regulated expression of microRNA-338-5p contributes to neuropathology in Alzheimer's disease. FASEB J. 33,4404–4417 (2019). www.fasebj.org.
AB - Alzheimer's disease (AD) is a leading cause of dementia. However, the mechanisms responsible for development of AD, especially for the sporadic variant, are still not clear. In our previous study, we discovered that a small noncoding RNA (miR-188-3p) targeting β-site amyloid precursor protein cleaving enzyme (BACE)-l, a key enzyme responsible for Aβ formation, plays an important role in the development of neuropathology in AD. In the present study, we identified that miR-338-5p, a new miRNA that also targets BACE1, contributes to AD neuropathology. We observed that expression of miR-338-5p was significantly down-regulated in the hippocampus of patients with AD and 5XFAD transgenic (TG) mice, an animal model of AD. Overexpression of miR-338-5p in the hippocampus of TG mice reduced BACE1 expression, Aβ formation, and neuroinflammation. Overexpression of miR-338-5p functionally prevented impairments in long-term synaptic plasticity, learning ability, and memory retention in TG mice. In addition, we provide evidence that down-regulated expression of miR-338-5p in AD is regulated through the NF-κB signaling pathway. Our results suggest that down-regulated expression of miR-338-5p plays an important role in the development of AD.—Qian, Q., Zhang, J., He, F.-P., Bao, W.-X., Zheng, T.-T., Zhou, D.-M., Pan, H.-Y., Zhang, H., Zhang, X.-Q., He, X., Sun, B.-G., Luo, B.-Y., Chen, C., Peng, G.-P. Down-regulated expression of microRNA-338-5p contributes to neuropathology in Alzheimer's disease. FASEB J. 33,4404–4417 (2019). www.fasebj.org.
KW - BACE1
KW - NF-κB
KW - epigenetics
KW - neuroinflammation
KW - noncoding small RNA
UR - http://www.scopus.com/inward/record.url?scp=85068584244&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068584244&partnerID=8YFLogxK
U2 - 10.1096/fj.201801846R
DO - 10.1096/fj.201801846R
M3 - Article
C2 - 30576233
AN - SCOPUS:85068584244
SN - 0892-6638
VL - 33
SP - 4404
EP - 4417
JO - FASEB Journal
JF - FASEB Journal
IS - 3
ER -