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DPP-4 inhibitor improves learning and memory deficits and AD-like neurodegeneration by modulating the GLP-1 signaling
Chen S, Zhou M, Sun J, Guo A, Fernando RL, Chen Y, Peng P, Zhao G et al.. Neuropharmacology, 2019-06-12
Topic: Gut, metabolism and diet
Glucagon-like peptide-1 (GLP-1) signaling in the brain plays an important role in the regulation of glucose metabolism, which is impaired in Alzheimer's disease (AD). Here, we detected the GLP-1 and GLP-1 receptor (GLP-1R) in AD human brain and APP/PS1/Tau transgenic (3xTg) mice brain, finding that they were both decreased in AD human and mice brain. Enhanced GLP-1 exerts its protective effects on AD, however, this is rapidly degraded into inactivated metabolites by dipeptidyl peptidase-4 (DPP-4), resulting in its extremely short half-time. DPP-4 inhibitors, thus, was applied to improve the level of GLP-1 and GLP-1R expression in the hippocampus and cortex of AD mice brains. It is also protected learning and memory and synaptic proteins, increased the O-Glycosylation and decreased abnormal phosphorylation of tau and neurofilaments (NFs), degraded intercellular β-amyloid (Aβ) accumulation and alleviated neurodegeneration related to GLP-1 signaling pathway.
Key findings
- Glucagon-like peptide-1 (GLP-1) signaling in the brain plays an important role in the regulation of glucose metabolism, which is impaired in Alzheimer's disease (AD).
- Here, we detected the GLP-1 and GLP-1 receptor (GLP-1R) in AD human brain and APP/PS1/Tau transgenic (3xTg) mice brain, finding that they were both decreased in AD human and mice brain.
- Enhanced GLP-1 exerts its protective effects on AD, however, this is rapidly degraded into inactivated metabolites by dipeptidyl peptidase-4 (DPP-4), resulting in its extremely short half-time.
- DPP-4 inhibitors, thus, was applied to improve the level of GLP-1 and GLP-1R expression in the hippocampus and cortex of AD mice brains.
- It is also protected learning and memory and synaptic proteins, increased the O-Glycosylation and decreased abnormal phosphorylation of tau and neurofilaments (NFs), degraded intercellular β-amyloid (Aβ) accumulation and alleviated neurodegeneration related to GLP-1 signaling pathway.
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Study details
- Evidence strengthLow
How this study scored 38/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 22 of the 58 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neuropharmacology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31199957) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 22 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 22 of the 58 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
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APA 7th
Chen, S., Zhou, M., Sun, J., Guo, A., Fernando, R. L., Chen, Y., et al. (2019). DPP-4 inhibitor improves learning and memory deficits and AD-like neurodegeneration by modulating the GLP-1 signaling. Neuropharmacology. https://doi.org/10.1016/j.neuropharm.2019.107668
Vancouver
Chen S, Zhou M, Sun J, Guo A, Fernando RL, Chen Y, et al. DPP-4 inhibitor improves learning and memory deficits and AD-like neurodegeneration by modulating the GLP-1 signaling. Neuropharmacology. 2019. doi:10.1016/j.neuropharm.2019.107668. PMID: 31199957.
BibTeX
@article{chen2019-31199957,
author = {Chen, S. and Zhou, M. and Sun, J. and Guo, A. and Fernando, R. L. and Chen, Y. and Peng, P. and Zhao, G. and others},
title = {{DPP-4 inhibitor improves learning and memory deficits and AD-like neurodegeneration by modulating the GLP-1 signaling}},
journal = {Neuropharmacology},
year = {2019},
doi = {10.1016/j.neuropharm.2019.107668},
pmid = {31199957},
url = {https://doi.org/10.1016/j.neuropharm.2019.107668}
}
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