A Class I HDAC Inhibitor BG45 Alleviates Cognitive Impairment through the CaMKII/ITPKA/Ca<sup>2+</sup> Signaling Pathway
Alzheimer’s disease (AD) seriously endangers the health and life of elderly individuals worldwide. However, despite all scientific efforts, at the moment there are no effective clinical treatment options for AD. In this work, the effect of the class I histone deacetylase inhibitor (HDACI) BG45 on sy...
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MDPI AG
2022-11-01
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| Online Access: | https://www.mdpi.com/1424-8247/15/12/1481 |
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| author | Jingyun Liu Chenghong Zhang Jiale Wang Yufei Huang Di Shen Yingqiu Hu Haiying Chu Xuebin Yu Liyuan Zhang Haiying Ma |
| author_facet | Jingyun Liu Chenghong Zhang Jiale Wang Yufei Huang Di Shen Yingqiu Hu Haiying Chu Xuebin Yu Liyuan Zhang Haiying Ma |
| author_sort | Jingyun Liu |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) seriously endangers the health and life of elderly individuals worldwide. However, despite all scientific efforts, at the moment there are no effective clinical treatment options for AD. In this work, the effect of the class I histone deacetylase inhibitor (HDACI) BG45 on synapse-related proteins was investigated in primary neurons from APP/PS1 transgenic mice. The results showed that BG45 can upregulate the expression of synaptotagmin-1 (SYT-1) and neurofilament light chain (NF-L) in primary neurons. In vivo, the APPswe/PS1dE9 (APP/PS1) transgenic mice were treated with BG45 (30 mg/kg) daily for 12 days. Behavioral testing of BG45-treated APP/PS1 mice showed improvements in learning and memory. BG45 can alleviate damage to the dendritic spine and reduce the deposition of Aβ. Similar to the in vitro results, synapse-related proteins in the prefrontal cortex were increased after BG45 treatment. Proteomic analysis results highlighted the differences in the biological processes of energy metabolism and calmodulin regulation in APP/PS1 mice with or without BG45 treatment. Further verification demonstrated that the effect of BG45 on synapses and learning and memory may involve the CaMKII/ITPKA/Ca<sup>2+</sup> pathway. These results suggest that class I HDACI BG45 might be a promising drug for the early clinical treatment of AD. |
| first_indexed | 2024-03-09T15:59:20Z |
| format | Article |
| id | doaj.art-680368d937f848f0a7650abbffbca2ec |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T15:59:20Z |
| publishDate | 2022-11-01 |
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| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-680368d937f848f0a7650abbffbca2ec2023-11-24T17:15:55ZengMDPI AGPharmaceuticals1424-82472022-11-011512148110.3390/ph15121481A Class I HDAC Inhibitor BG45 Alleviates Cognitive Impairment through the CaMKII/ITPKA/Ca<sup>2+</sup> Signaling PathwayJingyun Liu0Chenghong Zhang1Jiale Wang2Yufei Huang3Di Shen4Yingqiu Hu5Haiying Chu6Xuebin Yu7Liyuan Zhang8Haiying Ma9Department of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaDepartment of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaDepartment of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaDepartment of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaDepartment of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaDepartment of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaDepartment of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaDepartment of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaDepartment of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaDepartment of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaAlzheimer’s disease (AD) seriously endangers the health and life of elderly individuals worldwide. However, despite all scientific efforts, at the moment there are no effective clinical treatment options for AD. In this work, the effect of the class I histone deacetylase inhibitor (HDACI) BG45 on synapse-related proteins was investigated in primary neurons from APP/PS1 transgenic mice. The results showed that BG45 can upregulate the expression of synaptotagmin-1 (SYT-1) and neurofilament light chain (NF-L) in primary neurons. In vivo, the APPswe/PS1dE9 (APP/PS1) transgenic mice were treated with BG45 (30 mg/kg) daily for 12 days. Behavioral testing of BG45-treated APP/PS1 mice showed improvements in learning and memory. BG45 can alleviate damage to the dendritic spine and reduce the deposition of Aβ. Similar to the in vitro results, synapse-related proteins in the prefrontal cortex were increased after BG45 treatment. Proteomic analysis results highlighted the differences in the biological processes of energy metabolism and calmodulin regulation in APP/PS1 mice with or without BG45 treatment. Further verification demonstrated that the effect of BG45 on synapses and learning and memory may involve the CaMKII/ITPKA/Ca<sup>2+</sup> pathway. These results suggest that class I HDACI BG45 might be a promising drug for the early clinical treatment of AD.https://www.mdpi.com/1424-8247/15/12/1481Alzheimer’s diseaseproteomicshistone deacetylase inhibitorsynaptic plasticity |
| spellingShingle | Jingyun Liu Chenghong Zhang Jiale Wang Yufei Huang Di Shen Yingqiu Hu Haiying Chu Xuebin Yu Liyuan Zhang Haiying Ma A Class I HDAC Inhibitor BG45 Alleviates Cognitive Impairment through the CaMKII/ITPKA/Ca<sup>2+</sup> Signaling Pathway Pharmaceuticals Alzheimer’s disease proteomics histone deacetylase inhibitor synaptic plasticity |
| title | A Class I HDAC Inhibitor BG45 Alleviates Cognitive Impairment through the CaMKII/ITPKA/Ca<sup>2+</sup> Signaling Pathway |
| title_full | A Class I HDAC Inhibitor BG45 Alleviates Cognitive Impairment through the CaMKII/ITPKA/Ca<sup>2+</sup> Signaling Pathway |
| title_fullStr | A Class I HDAC Inhibitor BG45 Alleviates Cognitive Impairment through the CaMKII/ITPKA/Ca<sup>2+</sup> Signaling Pathway |
| title_full_unstemmed | A Class I HDAC Inhibitor BG45 Alleviates Cognitive Impairment through the CaMKII/ITPKA/Ca<sup>2+</sup> Signaling Pathway |
| title_short | A Class I HDAC Inhibitor BG45 Alleviates Cognitive Impairment through the CaMKII/ITPKA/Ca<sup>2+</sup> Signaling Pathway |
| title_sort | class i hdac inhibitor bg45 alleviates cognitive impairment through the camkii itpka ca sup 2 sup signaling pathway |
| topic | Alzheimer’s disease proteomics histone deacetylase inhibitor synaptic plasticity |
| url | https://www.mdpi.com/1424-8247/15/12/1481 |
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