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@ARTICLE{Li:285815,
author = {Li, Tao and Castro-Gomez, Mario Sergio and Botella Lucena,
Pablo and Vieira-Saecker, Ana and Schwartz, Stephanie and
Ding, Yingying and Deng, Yushuang and Gou, Maling and Stein,
Valentin and Golenbock, Douglas T and Latz, Eicke and
Heneka, Michael T},
title = {{I}nflammasome adaptor {ASC} promotes sustained
neuroinflammation and mild cognitive impairment in a
closed-head injury model.},
journal = {The journal of clinical investigation},
volume = {136},
number = {7},
issn = {0021-9738},
address = {Ann Arbor, Mich.},
publisher = {ASCJ},
reportid = {DZNE-2026-00351},
pages = {e199818},
year = {2026},
abstract = {Mild traumatic brain injury (mTBI) from a closed-head
injury (CHI) can lead to prevalent neuropsychiatric
disorders, including mood disorders and an increased risk
for neurodegenerative diseases and dementia. Inflammasomes
are molecular complexes crucial for neuroinflammation and
secondary damage after trauma, however their role in mild
CHI (mCHI) is poorly understood. In this study, we
investigate the cellular expression of inflammasome-related
genes and their functional significance in CHI models.
Single-cell RNA-seq analysis of cortical tissue after trauma
revealed selective expression of Asc (also known as Pycard),
which encodes the inflammasome adaptor apoptosis-associated
Speck-like protein containing a caspase recruitment domain
(ASC), predominantly in microglial clusters. Sustained
upregulation of inflammasome-related proteins, microglia
activation, and astrocyte reactivity persisted up to 21 days
in a model for mTBI, with significant reduction of this
pattern in Asc-/- mice. Importantly, mild cognitive
impairment induced after mCHI was largely abrogated in
Asc-/- mice. These findings suggest that ASC, as the primary
inflammasome adaptor, plays a critical role in sustaining
neuroinflammation and contributes to cognitive deficits
after mCHI. This study provides insights into the molecular
neuroinflammatory mechanisms underlying CHI, potentially
informing future therapeutic strategies.},
keywords = {Animals / CARD Signaling Adaptor Proteins: genetics / CARD
Signaling Adaptor Proteins: metabolism / Mice / Cognitive
Dysfunction: pathology / Cognitive Dysfunction: metabolism /
Cognitive Dysfunction: genetics / Cognitive Dysfunction:
etiology / Inflammasomes: genetics / Inflammasomes:
metabolism / Disease Models, Animal / Mice, Knockout /
Neuroinflammatory Diseases: pathology / Neuroinflammatory
Diseases: metabolism / Neuroinflammatory Diseases: genetics
/ Neuroinflammatory Diseases: etiology / Male / Brain
Concussion: pathology / Brain Concussion: genetics / Brain
Concussion: metabolism / Microglia: pathology / Microglia:
metabolism / Mice, Inbred C57BL / Dementia (Other) /
Inflammation (Other) / Innate immunity (Other) /
Neuroscience (Other) / Transcriptomics (Other) / CARD
Signaling Adaptor Proteins (NLM Chemicals) / Inflammasomes
(NLM Chemicals) / Pycard protein, mouse (NLM Chemicals)},
cin = {AG Ehninger},
ddc = {610},
cid = {I:(DE-2719)1013005},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41734021},
pmc = {pmc:PMC13038205},
doi = {10.1172/JCI199818},
url = {https://pub.dzne.de/record/285815},
}