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Research Article
Hongkun Wu
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7275-3384
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This work is licensed under a CC BY 4.0 License. Read Full License
Accumulation of amyloid-β (Aβ) in the brain is a central component of pathology in Alzheimer’s disease. A growing number of evidences demonstrate close associations between periodontal pathogens including Porphyromonas gingivalis (P. gingivalis) and Treponema denticola (T. denticola) and AD. However, the effect and mechanisms of T. denticola on accumulation of Aβ remain to be unclear. In this study, we demonstrated that T. denticola was able to enter brain and act directly on nerve cells resulting in intra and extracellular Aβ1−40 and Aβ1−42 accumulation in the hippocampus of C57BL/6 mice by selectively activating both β-secretase and γ-secretase. Furthermore, both KMI1303, an inhibitor of β- secretase, as well as DAPT, an inhibitor of γ- secretase were found to be able to inhibit the effect of T. denticola on Aβ accumulation in N2a neuronal cells. Overall, it is concluded that T. denticola increases the expression of Aβ1−42 and Aβ1−40 by its regulation on beta-site amyloid precursor protein cleaving enzyme-1 and Presenilin 1.
Keywords
Treponema denticola, Alzheimer’s disease, amyloid-β, BACE1, Presenilin 1
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View the published article at Journal of Molecular Neuroscience.
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Posted 15 Feb, 2021
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A new preprint design is coming!
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See the published version of this preprint at Journal of Molecular Neuroscience.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Hongkun Wu
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7275-3384
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Journal of Molecular Neuroscience.
Version 1
Posted 15 Feb, 2021
No community comments so far
Reviews received
Received 16 Feb, 2021
Reviewers invited
Invitations sent on 09 Feb, 2021
Editor assigned
On 08 Feb, 2021
First submitted
On 08 Feb, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Journal of Molecular Neuroscience.
Accumulation of amyloid-β (Aβ) in the brain is a central component of pathology in Alzheimer’s disease. A growing number of evidences demonstrate close associations between periodontal pathogens including Porphyromonas gingivalis (P. gingivalis) and Treponema denticola (T. denticola) and AD. However, the effect and mechanisms of T. denticola on accumulation of Aβ remain to be unclear. In this study, we demonstrated that T. denticola was able to enter brain and act directly on nerve cells resulting in intra and extracellular Aβ1−40 and Aβ1−42 accumulation in the hippocampus of C57BL/6 mice by selectively activating both β-secretase and γ-secretase. Furthermore, both KMI1303, an inhibitor of β- secretase, as well as DAPT, an inhibitor of γ- secretase were found to be able to inhibit the effect of T. denticola on Aβ accumulation in N2a neuronal cells. Overall, it is concluded that T. denticola increases the expression of Aβ1−42 and Aβ1−40 by its regulation on beta-site amyloid precursor protein cleaving enzyme-1 and Presenilin 1.
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
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