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O-GlcNAc modification of small heat shock proteins enhances their anti-amyloid chaperone activity
Balana AT, Levine PM, Craven TW, Mukherjee S, Pedowitz NJ, Moon SP, Takahashi TT, Becker CFW et al.. Nature chemistry, 2021-03-15
Topic: Brain proteins, microglia and lab models
A major role for the intracellular post-translational modification O-GlcNAc appears to be the inhibition of protein aggregation. Most of the previous studies in this area focused on O-GlcNAc modification of the amyloid-forming proteins themselves. Here we used synthetic protein chemistry to discover that O-GlcNAc also activates the anti-amyloid activity of certain small heat shock proteins (sHSPs), a potentially more important modification event that can act broadly and substoichiometrically. More specifically, we found that O-GlcNAc increases the ability of sHSPs to block the amyloid formation of both α-synuclein and Aβ(1-42). Mechanistically, we show that O-GlcNAc near the sHSP IXI-domain prevents its ability to intramolecularly compete with substrate binding. Finally, we found that, although O-GlcNAc levels are globally reduced in Alzheimer's disease brains, the modification of relevant sHSPs is either maintained or increased, which suggests a mechanism to maintain these potentially protective O-GlcNAc modifications. Our results have important implications for neurodegenerative diseases associated with amyloid formation and potentially other areas of sHSP biology.
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APA 7th
Balana, A. T., Levine, P. M., Craven, T. W., Mukherjee, S., Pedowitz, N. J., Moon, S. P., et al. (2021). O-GlcNAc modification of small heat shock proteins enhances their anti-amyloid chaperone activity. Nature chemistry. https://doi.org/10.1038/s41557-021-00648-8
Vancouver
Balana AT, Levine PM, Craven TW, Mukherjee S, Pedowitz NJ, Moon SP, et al. O-GlcNAc modification of small heat shock proteins enhances their anti-amyloid chaperone activity. Nature chemistry. 2021. doi:10.1038/s41557-021-00648-8. PMID: 33723378.
BibTeX
@article{balana2021-33723378,
author = {Balana, A. T. and Levine, P. M. and Craven, T. W. and Mukherjee, S. and Pedowitz, N. J. and Moon, S. P. and Takahashi, T. T. and Becker, C. F. W. and others},
title = {{O-GlcNAc modification of small heat shock proteins enhances their anti-amyloid chaperone activity}},
journal = {Nature chemistry},
year = {2021},
doi = {10.1038/s41557-021-00648-8},
pmid = {33723378},
url = {https://doi.org/10.1038/s41557-021-00648-8}
}
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Key findings
- More specifically, we found that O-GlcNAc increases the ability of sHSPs to block the amyloid formation of both α-synuclein and Aβ(1-42).
- Finally, we found that, although O-GlcNAc levels are globally reduced in Alzheimer's disease brains, the modification of relevant sHSPs is either maintained or increased, which suggests a mechanism to maintain these potentially protective O-GlcNAc modifications.
- Our results have important implications for neurodegenerative diseases associated with amyloid formation and potentially other areas of sHSP biology.
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Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / 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 multicenter collaboration, so those were left out: it earned 25 of the 58 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Nature chemistry) |
| 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 | 3 / 5 | 2021 — within 6 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) |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33723378) |
| Free to read | 2 / 2 | Free to read |
| Points | 25 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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