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@ARTICLE{GmezPascual:285354,
author = {Gómez-Pascual, Alicia and Glikman, Dow M and Ng, Hui Xin
and Tomkins, James E and Lu, Lu and Xu, Ying and Ashbrook,
David G and Kaczorowski, Catherine and Kempermann, Gerd and
Killmar, John and Mozhui, Khyobeni and Ohlenschläger,
Oliver and Aebersold, Rudolf and Ingram, Donald K and
Williams, Evan G and Jucker, Mathias and Overall, Rupert W
and Williams, Robert W and de Bakker, Dennis E M},
title = {{T}he {S}marcal1-{U}sp37 locus modulates glycogen
aggregation in astrocytes of the aged hippocampus.},
journal = {Cell systems},
volume = {17},
number = {2},
issn = {2405-4712},
address = {Maryland Heights, MO},
publisher = {Elsevier},
reportid = {DZNE-2026-00220},
pages = {101488},
year = {2026},
abstract = {In aged humans and mice, hypobranched glycogen aggregates,
known as polyglucosan bodies (PGBs), accumulate in
hippocampal astrocytes. While PGBs are linked to cognitive
decline in neurological diseases, they remain largely
unstudied in the context of typical aging. We show that PGBs
arise in autophagy-dysregulated astrocytes in the aged
hippocampus, with substantial variation among 32 inbred BXD
mouse strains. Genetic mapping through quantitative trait
locus analysis identified a major locus (Pgb1) that
modulates hippocampal PGB burden. Extensive transcriptomic
and proteomic datasets were produced for the aged
hippocampus of the BXD family to investigate the mechanism
by which the Pgb1 locus modulates PGB burden. We identified
that Pgb1 contains allelic Smarcal1 and Usp37 variants and
influences PGB burden through trans-regulation of mRNA and
protein expression levels, including abundance of
glycogen-mobilizing factor PYGB. Furthermore, comprehensive
phenome-wide association scans, transcriptomic analyses, and
direct behavioral testing demonstrated that cognition
remains intact despite age-related PGB burden. A record of
this paper's transparent peer review process is included in
the supplemental information.},
keywords = {Animals / Hippocampus: metabolism / Glycogen: metabolism /
Mice / Astrocytes: metabolism / Aging: genetics / Aging:
metabolism / Male / Quantitative Trait Loci: genetics /
Mice, Inbred C57BL / Humans / Glucans / astrocytes (Other) /
brain aging (Other) / glycogen metabolism (Other) /
hippocampus (Other) / polyglucosan bodies (Other) /
quantitative trait locus analysis (Other) / system genetics
(Other) / Glycogen (NLM Chemicals) / polyglucosan (NLM
Chemicals) / Glucans (NLM Chemicals)},
cin = {AG Jucker / AG Kempermann},
ddc = {570},
cid = {I:(DE-2719)1210001 / I:(DE-2719)1710001},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41633365},
doi = {10.1016/j.cels.2025.101488},
url = {https://pub.dzne.de/record/285354},
}