biostudies-literatureQian QNational Institute of Neurological Disorders and StrokeNational Basic Research Program of ChinaZhejiang Chinese Medical UniversityNIA NIH HHSNational Natural Science Foundation of ChinaNINDS NIH HHSNational Institutes of Health4404-4417https://www.ebi.ac.uk/biostudies/studies/S-EPMC6404576biostudies-literatureUnknown33(3)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)-1, 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 journal : official publication of the Federation of American Societies for Experimental BiologyDown-regulated expression of microRNA-338-5p contributes to neuropathology in Alzheimer's disease.PMC6404576R01 NS0768152018ZR0481471284R01 AG058621R01NS076815R01AG0586212016YFC1306402Zhang JLuo BYZhang HHe FPChen CZhou DMPeng GPHe XBao WXZheng TTZhang XQPan HYQian QSun BGfalseDown-regulated expression of microRNA-338-5p contributes to neuropathology in Alzheimer's disease.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)-1, 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.2019-01-01T00:00:00Z2019 Mar2022-02-11T16:03:09.961Z2020-11-07T11:12:10ZS-EPMC64045763057623310.1096/fj.201801846R10.1096/fj.201801846r