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NLRP3-directed antisense oligonucleotides reduce microglial immunoactivities in vitro
Charlotte Braatz, Max P Komes, Kishore Aravind Ravichandran, Matheus Garcia de Fragas, Angelika Griep, Stephanie Schwartz, Róisín M McManus, Michael T Heneka. Journal of neurochemistry, 2023-03-17
Topic: Inflammation, microglia and astrocytes
Alzheimer's disease (AD) is associated with the cerebral deposition of Amyloid-β (Aβ) peptide, which leads to NLRP3 inflammasome activation and subsequent release of interleukin-1β (IL-1β) and interleukin-18 (IL-18). NLRP3 reduction has been found to increase microglial clearance, protect from synapse loss, and suppress both the changes to synaptic plasticity and spatial memory dysfunction observed in murine AD models. Here, we test whether NLRP3-directed antisense oligonucleotides (ASOs) can be harnessed as immune modulators in primary murine microglia and human THP-1 cells. NLRP3 mRNA degradation was achieved at 72 h of ASO treatment in primary murine microglia. Consequently, NLRP3-directed ASOs significantly reduced the levels of cleaved caspase-1 and mature IL-1β when microglia were either activated by LPS and nigericin or LPS and Aβ. In human THP-1 cells NLRP3-targeted ASOs also significantly reduced the LPS plus nigericin- or LPS plus Aβ-induced release of mature IL-1β. Together, NLRP3-directed ASOs can suppress NLRP3 inflammasome activity and subsequent release of IL-1β in primary murine microglia and THP-1 cells. ASOs may represent a new and alternative approach to modulate NLRP3 inflammasome activation in neurodegenerative diseases, in addition to attempts to inhibit the complex pharmacologically.
Key findings
- Alzheimer's disease (AD) is associated with the cerebral deposition of Amyloid-β (Aβ) peptide, which leads to NLRP3 inflammasome activation and subsequent release of interleukin-1β (IL-1β) and interleukin-18 (IL-18).
- Consequently, NLRP3-directed ASOs significantly reduced the levels of cleaved caspase-1 and mature IL-1β when microglia were either activated by LPS and nigericin or LPS and Aβ.
- In human THP-1 cells NLRP3-targeted ASOs also significantly reduced the LPS plus nigericin- or LPS plus Aβ-induced release of mature IL-1β.
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 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, multi-centre collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neurochemistry) |
| 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 | 4 / 5 | 2024 — within 3 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 “in vitro”) — 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 36799439) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Braatz, C., Komes, M. P., Ravichandran, K. A., de Fragas, M. G., Griep, A., Schwartz, S., et al. (2024). NLRP3-directed antisense oligonucleotides reduce microglial immunoactivities in vitro. Journal of neurochemistry. https://doi.org/10.1111/jnc.15778
Vancouver
Braatz C, Komes MP, Ravichandran KA, de Fragas MG, Griep A, Schwartz S, et al. NLRP3-directed antisense oligonucleotides reduce microglial immunoactivities in vitro. Journal of neurochemistry. 2024. doi:10.1111/jnc.15778. PMID: 36799439.
BibTeX
@article{braatz2024-36799439,
author = {Braatz, Charlotte and Komes, Max P and Ravichandran, Kishore Aravind and de Fragas, Matheus Garcia and Griep, Angelika and Schwartz, Stephanie and McManus, Róisín M and Heneka, Michael T},
title = {{NLRP3-directed antisense oligonucleotides reduce microglial immunoactivities in vitro}},
journal = {Journal of neurochemistry},
year = {2024},
doi = {10.1111/jnc.15778},
pmid = {36799439},
url = {https://doi.org/10.1111/jnc.15778}
}