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Galectin-3 promotes Aβ oligomerization and Aβ toxicity in a mouse model of Alzheimer's disease
Tao CC, Cheng KM, Ma YL, Hsu WL, Chen YC, Fuh JL, Lee WJ, Chao CC et al.. Cell death and differentiation, 2019-05-24
Topic: Brain proteins, microglia and lab models
Amyloid-β (Aβ) oligomers largely initiate the cascade underlying the pathology of Alzheimer's disease (AD). Galectin-3 (Gal-3), which is a member of the galectin protein family, promotes inflammatory responses and enhances the homotypic aggregation of cancer cells. Here, we examined the role and action mechanism of Gal-3 in Aβ oligomerization and Aβ toxicities. Wild-type (WT) and Gal-3-knockout (KO) mice, APP/PS1;WT mice, APP/PS1;Gal-3 +/- mice and brain tissues from normal subjects and AD patients were used. We found that Aβ oligomerization is reduced in Gal-3 KO mice injected with Aβ, whereas overexpression of Gal-3 enhances Aβ oligomerization in the hippocampi of Aβ-injected mice. Gal-3 expression shows an age-dependent increase that parallels endogenous Aβ oligomerization in APP/PS1 mice. Moreover, Aβ oligomerization, Iba1 expression, GFAP expression and amyloid plaque accumulation are reduced in APP/PS1;Gal-3 +/- mice compared with APP/PS1;WT mice. APP/PS1;Gal-3 +/- mice also show better acquisition and retention performance compared to APP/PS1;WT mice. In studying the mechanism underlying Gal-3-promoted Aβ oligomerization, we found that Gal-3 primarily co-localizes with Iba1, and that microglia-secreted Gal-3 directly interacts with Aβ. Gal-3 also interacts with triggering receptor expressed on myeloid cells-2, which then mediates the ability of Gal-3 to activate microglia for further Gal-3 expression. Immunohistochemical analyses show that the distribution of Gal-3 overlaps with that of endogenous Aβ in APP/PS1 mice and partially overlaps with that of amyloid plaque. Moreover, the expression of the Aβ-degrading enzyme, neprilysin, is increased in Gal-3 KO mice and this is associated with enhanced integrin-mediated signaling. Consistently, Gal-3 expression is also increased in the frontal lobe of AD patients, in parallel with Aβ oligomerization. Because Gal-3 expression is dramatically increased as early as 3 months of age in APP/PS1 mice and anti-Aβ oligomerization is believed to protect against Aβ toxicity, Gal-3 could be considered a novel therapeutic target in efforts to combat AD.
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APA 7th
Tao, C. C., Cheng, K. M., Ma, Y. L., Hsu, W. L., Chen, Y. C., Fuh, J. L., et al. (2020). Galectin-3 promotes Aβ oligomerization and Aβ toxicity in a mouse model of Alzheimer's disease. Cell death and differentiation. https://doi.org/10.1038/s41418-019-0348-z
Vancouver
Tao CC, Cheng KM, Ma YL, Hsu WL, Chen YC, Fuh JL, et al. Galectin-3 promotes Aβ oligomerization and Aβ toxicity in a mouse model of Alzheimer's disease. Cell death and differentiation. 2020. doi:10.1038/s41418-019-0348-z. PMID: 31127200.
BibTeX
@article{tao2020-31127200,
author = {Tao, C. C. and Cheng, K. M. and Ma, Y. L. and Hsu, W. L. and Chen, Y. C. and Fuh, J. L. and Lee, W. J. and Chao, C. C. and others},
title = {{Galectin-3 promotes Aβ oligomerization and Aβ toxicity in a mouse model of Alzheimer's disease}},
journal = {Cell death and differentiation},
year = {2020},
doi = {10.1038/s41418-019-0348-z},
pmid = {31127200},
url = {https://doi.org/10.1038/s41418-019-0348-z}
}
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Key findings
- We found that Aβ oligomerization is reduced in Gal-3 KO mice injected with Aβ, whereas overexpression of Gal-3 enhances Aβ oligomerization in the hippocampi of Aβ-injected mice.
- Moreover, Aβ oligomerization, Iba1 expression, GFAP expression and amyloid plaque accumulation are reduced in APP/PS1;Gal-3 +/- mice compared with APP/PS1;WT mice.
- APP/PS1;Gal-3 +/- mice also show better acquisition and retention performance compared to APP/PS1;WT mice.
- In studying the mechanism underlying Gal-3-promoted Aβ oligomerization, we found that Gal-3 primarily co-localizes with Iba1, and that microglia-secreted Gal-3 directly interacts with Aβ.
- Moreover, the expression of the Aβ-degrading enzyme, neprilysin, is increased in Gal-3 KO mice and this is associated with enhanced integrin-mediated signaling.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported 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 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell death and differentiation) |
| 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 | 2020 — 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 | Laboratory or animal study (title names “mouse”) — scores zero |
| 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 31127200) |
| Free to read | 2 / 2 | Free to read |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
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