Cofilin 2 Acts as an Inflammatory Linker Between Chronic Periodontitis and Alzheimer’s Disease in Amyloid Precursor Protein/Presenilin 1 Mice
Increasing evidence has shown a correlation between chronic periodontitis (CP) and Alzheimer’s disease (AD). Nevertheless, there is still a lack of direct evidence, and especially key molecules to connect the two diseases. This study aims to investigate potential protein links between CP and AD with...
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2021-09-01
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doaj-f6dfdcc6aecb4bdaa935cd25c4f53a222021-09-30T05:13:06ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992021-09-011410.3389/fnmol.2021.728184728184Cofilin 2 Acts as an Inflammatory Linker Between Chronic Periodontitis and Alzheimer’s Disease in Amyloid Precursor Protein/Presenilin 1 MiceQing Zeng0Qin Fang1Xincai Zhou2Hongfa Yang3Yang Dou4Wenhao Zhang5Pu Gong6Xianfang Rong7Department of Stomatology, Shenzhen Baoan Women’s and Children’s Hospital, Jinan University, Shenzhen, ChinaDepartment of Stomatology, Shenzhen Baoan Women’s and Children’s Hospital, Jinan University, Shenzhen, ChinaDepartment of Stomatology, Shenzhen Baoan Women’s and Children’s Hospital, Jinan University, Shenzhen, ChinaDepartment of Cardiology, The Second Affiliated Hospital of University of South China, Hengyang, ChinaDepartment of Stomatology, Shenzhen Baoan Women’s and Children’s Hospital, Jinan University, Shenzhen, ChinaDepartment of Stomatology, Shenzhen Baoan Women’s and Children’s Hospital, Jinan University, Shenzhen, ChinaDepartment of Stomatology, Shenzhen Baoan Women’s and Children’s Hospital, Jinan University, Shenzhen, ChinaDepartment of Stomatology, Shenzhen Baoan Women’s and Children’s Hospital, Jinan University, Shenzhen, ChinaIncreasing evidence has shown a correlation between chronic periodontitis (CP) and Alzheimer’s disease (AD). Nevertheless, there is still a lack of direct evidence, and especially key molecules to connect the two diseases. This study aims to investigate potential protein links between CP and AD within the inflammatory aspect. The hippocampus of CP model mice and controls were collected, and changes in protein expression were evaluated using two-dimensional differential in-gel electrophoresis (2D-DIGE) analysis combined with liquid chromatography tandem mass spectrometry. A total of 15 differentially expressed proteins were identified in CP model mice, as compared with the controls. Among them, S100-A9, transthyretin, Cofilin 2, peroxiredoxin 2, and lipocalin-2 were validated by Western blot according to their dual function both in inflammation and AD. Based on 2D-DIGE analysis, CP animal model had higher levels of S100-A9, Cofilin 2, peroxiredoxin 2, and lipocalin-2 compared to controls. The level of Cofilin 2, one of the well-established proteins in the pathology of AD, was strongly correlated with the time course of CP pathology, indicating a specific molecular correlation between CP and AD. Moreover, the in vivo results showed the level of Cofilin 2 increased significantly along with a prominent increase of the phosphorylation of protein phosphatase 2 (PP2A) and tau protein in the cell lysates of Porphyromonas gingivalis (P.g-LPS)-treated SK-N-SH APPwt cells. Cofilin 2 inhibition resulted in a sharp decrease in PP2A dependent of tau phosphorylation. Furthermore, tumor growth factor (TGF)-β1 was one of the most important inflammatory cytokines for the Pg-LPS-induced Cofilin 2 upregulation in SK-N-SH APPwt cells. These results showed inflammation served as the bond between CP and AD, whereas inflammatory related proteins could be the key linkers between the two diseases. Determining the association between CP and AD at the molecular mechanism will not only hold the direct evidence of the association between the two diseases but also provide a new way of preventing and treating AD: the effective prevention and treatment of CP could serve as a useful method to alleviate the development of AD.https://www.frontiersin.org/articles/10.3389/fnmol.2021.728184/fullchronic periodontitisAlzheimer’s disease2D-DIGECofilin 2neuroinflammation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qing Zeng Qin Fang Xincai Zhou Hongfa Yang Yang Dou Wenhao Zhang Pu Gong Xianfang Rong |
spellingShingle |
Qing Zeng Qin Fang Xincai Zhou Hongfa Yang Yang Dou Wenhao Zhang Pu Gong Xianfang Rong Cofilin 2 Acts as an Inflammatory Linker Between Chronic Periodontitis and Alzheimer’s Disease in Amyloid Precursor Protein/Presenilin 1 Mice Frontiers in Molecular Neuroscience chronic periodontitis Alzheimer’s disease 2D-DIGE Cofilin 2 neuroinflammation |
author_facet |
Qing Zeng Qin Fang Xincai Zhou Hongfa Yang Yang Dou Wenhao Zhang Pu Gong Xianfang Rong |
author_sort |
Qing Zeng |
title |
Cofilin 2 Acts as an Inflammatory Linker Between Chronic Periodontitis and Alzheimer’s Disease in Amyloid Precursor Protein/Presenilin 1 Mice |
title_short |
Cofilin 2 Acts as an Inflammatory Linker Between Chronic Periodontitis and Alzheimer’s Disease in Amyloid Precursor Protein/Presenilin 1 Mice |
title_full |
Cofilin 2 Acts as an Inflammatory Linker Between Chronic Periodontitis and Alzheimer’s Disease in Amyloid Precursor Protein/Presenilin 1 Mice |
title_fullStr |
Cofilin 2 Acts as an Inflammatory Linker Between Chronic Periodontitis and Alzheimer’s Disease in Amyloid Precursor Protein/Presenilin 1 Mice |
title_full_unstemmed |
Cofilin 2 Acts as an Inflammatory Linker Between Chronic Periodontitis and Alzheimer’s Disease in Amyloid Precursor Protein/Presenilin 1 Mice |
title_sort |
cofilin 2 acts as an inflammatory linker between chronic periodontitis and alzheimer’s disease in amyloid precursor protein/presenilin 1 mice |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Neuroscience |
issn |
1662-5099 |
publishDate |
2021-09-01 |
description |
Increasing evidence has shown a correlation between chronic periodontitis (CP) and Alzheimer’s disease (AD). Nevertheless, there is still a lack of direct evidence, and especially key molecules to connect the two diseases. This study aims to investigate potential protein links between CP and AD within the inflammatory aspect. The hippocampus of CP model mice and controls were collected, and changes in protein expression were evaluated using two-dimensional differential in-gel electrophoresis (2D-DIGE) analysis combined with liquid chromatography tandem mass spectrometry. A total of 15 differentially expressed proteins were identified in CP model mice, as compared with the controls. Among them, S100-A9, transthyretin, Cofilin 2, peroxiredoxin 2, and lipocalin-2 were validated by Western blot according to their dual function both in inflammation and AD. Based on 2D-DIGE analysis, CP animal model had higher levels of S100-A9, Cofilin 2, peroxiredoxin 2, and lipocalin-2 compared to controls. The level of Cofilin 2, one of the well-established proteins in the pathology of AD, was strongly correlated with the time course of CP pathology, indicating a specific molecular correlation between CP and AD. Moreover, the in vivo results showed the level of Cofilin 2 increased significantly along with a prominent increase of the phosphorylation of protein phosphatase 2 (PP2A) and tau protein in the cell lysates of Porphyromonas gingivalis (P.g-LPS)-treated SK-N-SH APPwt cells. Cofilin 2 inhibition resulted in a sharp decrease in PP2A dependent of tau phosphorylation. Furthermore, tumor growth factor (TGF)-β1 was one of the most important inflammatory cytokines for the Pg-LPS-induced Cofilin 2 upregulation in SK-N-SH APPwt cells. These results showed inflammation served as the bond between CP and AD, whereas inflammatory related proteins could be the key linkers between the two diseases. Determining the association between CP and AD at the molecular mechanism will not only hold the direct evidence of the association between the two diseases but also provide a new way of preventing and treating AD: the effective prevention and treatment of CP could serve as a useful method to alleviate the development of AD. |
topic |
chronic periodontitis Alzheimer’s disease 2D-DIGE Cofilin 2 neuroinflammation |
url |
https://www.frontiersin.org/articles/10.3389/fnmol.2021.728184/full |
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