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.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
Article
Seung-Yong Seong
Seoul Natonal University
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Amyloid β (Aβ) and/or ATP activates NLRP3 inflammasome (N3I) by P2 × 7R ion channel of microglia, which is crucial in neuroinflammation shown in Alzheimer’s disease (AD). Due to polymorphisms, subtypes, and ubiquitous expression of P2 × 7R, inhibition of P2 × 7R has not been effective for AD. We first report that GPCR19 is a prerequisite for P2 × 7R-mediated N3I activation and Taurodeoxycholate (TDCA), a GPCR19 ligand, inhibited the priming phase of N3I activation, suppressed P2 × 7R expression and P2 × 7R-mediated Ca++ mobilization, and N3I oligomerization which is essential for production of IL-1β/IL-18. Further, TDCA increased expression of scavenger receptor (SR) A, enhanced phagocytosis of Aβ, and decreased Aβ plaque numbers in the brain of 5x Familial Alzheimer’s disease (5xFAD) mice. TDCA also reduced microgliosis, prevented neuronal loss, and improved memory function of 5xFAD mice. The pleiotropic roles of GPCR19 in P2 × 7-mediated N3I activation suggest that targeting GPCR19 might resolve neuroinflammation in AD patients.
Keywords
Taurodeoxycholate, GPCR19, P2X7R, Alzheimer’s disease, Neuroinflammation, Inflammasome
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Yes there is potential Competing Interest. The patent “Pharmaceutical composition for prevention, treatment, or delay of Alzheimer's disease or dementia containing G protein-coupled receptor 19 agent as active ingredient: CN106794189, EP3248603, ES2750839, IN201747003504, JP2017523982, KR1020150095951, US20180104261” was invented by Seong et.al. and applied by Seoul National University R&DB Foundation. The exclusive license for the patent was transferred from SNU R&DB to Shaperon Inc. Dr S.Y. Seong is a founder of Shaperon Inc. and the current CEO.
This is a list of supplementary files associated with this preprint. Click to download.
- AlzMainSFigures201029.pptx
Supplementary Figure
- AlzMainSFigures201029.pptx
Supplementary Figure
- AlzMainSFigures201029.pptx
Supplementary Figure
Loading...
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 02 Dec, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
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.
Article
Seung-Yong Seong
Seoul Natonal University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 02 Dec, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Amyloid β (Aβ) and/or ATP activates NLRP3 inflammasome (N3I) by P2 × 7R ion channel of microglia, which is crucial in neuroinflammation shown in Alzheimer’s disease (AD). Due to polymorphisms, subtypes, and ubiquitous expression of P2 × 7R, inhibition of P2 × 7R has not been effective for AD. We first report that GPCR19 is a prerequisite for P2 × 7R-mediated N3I activation and Taurodeoxycholate (TDCA), a GPCR19 ligand, inhibited the priming phase of N3I activation, suppressed P2 × 7R expression and P2 × 7R-mediated Ca++ mobilization, and N3I oligomerization which is essential for production of IL-1β/IL-18. Further, TDCA increased expression of scavenger receptor (SR) A, enhanced phagocytosis of Aβ, and decreased Aβ plaque numbers in the brain of 5x Familial Alzheimer’s disease (5xFAD) mice. TDCA also reduced microgliosis, prevented neuronal loss, and improved memory function of 5xFAD mice. The pleiotropic roles of GPCR19 in P2 × 7-mediated N3I activation suggest that targeting GPCR19 might resolve neuroinflammation in AD patients.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Yes there is potential Competing Interest. The patent “Pharmaceutical composition for prevention, treatment, or delay of Alzheimer's disease or dementia containing G protein-coupled receptor 19 agent as active ingredient: CN106794189, EP3248603, ES2750839, IN201747003504, JP2017523982, KR1020150095951, US20180104261” was invented by Seong et.al. and applied by Seoul National University R&DB Foundation. The exclusive license for the patent was transferred from SNU R&DB to Shaperon Inc. Dr S.Y. Seong is a founder of Shaperon Inc. and the current CEO.
This is a list of supplementary files associated with this preprint. Click to download.
- AlzMainSFigures201029.pptx
Supplementary Figure
- AlzMainSFigures201029.pptx
Supplementary Figure
- AlzMainSFigures201029.pptx
Supplementary Figure
Loading...