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@ARTICLE{Braatz:257344,
author = {Braatz, Charlotte and Komes, Max and Ravichandran, Kishore
and Garcia de Fragas, Matheus and Griep, Angelika and
Schwartz, Stephanie and McManus, Roisin and Heneka, Michael
T},
title = {{NLRP}3-directed antisense oligonucleotides reduce
microglial immunoactivities in vitro.},
journal = {Journal of neurochemistry},
volume = {168},
number = {10},
issn = {0022-3042},
address = {Oxford},
publisher = {Wiley-Blackwell},
reportid = {DZNE-2023-00413},
pages = {3467 - 3481},
year = {2024},
abstract = {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.},
keywords = {Microglia: metabolism / Microglia: drug effects / Animals /
NLR Family, Pyrin Domain-Containing 3 Protein: metabolism /
Humans / Mice / Oligonucleotides, Antisense: pharmacology /
Mice, Inbred C57BL / Amyloid beta-Peptides: metabolism /
Interleukin-1beta: metabolism / Inflammasomes: metabolism /
THP-1 Cells / Cells, Cultured / Alzheimer's disease (Other)
/ Aβ (Other) / NLRP3 inflammasome (Other) / antisense
oligonucleotides (Other) / innate immunity (Other) /
microglia (Other) / neuroinflammation (Other)},
cin = {Biomarker / AG Heneka},
ddc = {610},
cid = {I:(DE-2719)1011301 / I:(DE-2719)1011303},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36799439},
doi = {10.1111/jnc.15778},
url = {https://pub.dzne.de/record/257344},
}