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@ARTICLE{Yazar:259245,
author = {Yazar, Volkan and Kühlwein, Julia and Knehr, Antje and
Grozdanov, Veselin and Ekici, Arif B and Ludolph, Albert C
and Danzer, Karin M},
title = {{I}mpaired {ATF}3 signaling involves {SNAP}25 in {SOD}1
mutant {ALS} patients.},
journal = {Scientific reports},
volume = {13},
number = {1},
issn = {2045-2322},
address = {[London]},
publisher = {Macmillan Publishers Limited, part of Springer Nature},
reportid = {DZNE-2023-00746},
pages = {12019},
year = {2023},
abstract = {Epigenetic remodeling is emerging as a critical process for
several neurodegenerative diseases, including amyotrophic
lateral sclerosis (ALS). Genetics alone fails to explain the
etiology of ALS, the investigation of the epigenome might
therefore provide novel insights into the molecular
mechanisms of the disease. In this study, we interrogated
the epigenetic landscape in peripheral blood mononuclear
cells (PBMCs) of familial ALS (fALS) patients with either
chromosome 9 open reading frame 72 (C9orf72) or superoxide
dismutase 1 (SOD1) mutation and aimed to identify key
epigenetic footprints of the disease. To this end, we used
an integrative approach that combines chromatin
immunoprecipitation targeting H3K27me3 (ChIP-Seq) with the
matching gene expression data to gain new insights into the
likely impact of blood-specific chromatin remodeling on
ALS-related molecular mechanisms. We demonstrated that one
of the hub molecules that modulates changes in PBMC
transcriptome in SOD1-mutant ALS patients is ATF3, which has
been previously reported in an SOD1G93A mouse model. We also
identified potential suppression of SNAP25, with impaired
ATF3 signaling in SOD1-mutant ALS blood. Together, our study
shed light on the mechanistic underpinnings of SOD1
mutations in ALS.},
keywords = {Animals / Mice / Amyotrophic Lateral Sclerosis: genetics /
Amyotrophic Lateral Sclerosis: metabolism / Leukocytes,
Mononuclear: metabolism / Mice, Transgenic / Mutation /
Superoxide Dismutase: genetics / Superoxide Dismutase:
metabolism / Superoxide Dismutase-1: genetics / Superoxide
Dismutase (NLM Chemicals) / Superoxide Dismutase-1 (NLM
Chemicals) / SNAP25 protein, human (NLM Chemicals) / SOD1
protein, human (NLM Chemicals)},
cin = {AG Danzer / Clinical Study Center Ulm},
ddc = {600},
cid = {I:(DE-2719)5000072 / I:(DE-2719)5000077},
pnm = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC10368635},
pubmed = {pmid:37491426},
doi = {10.1038/s41598-023-38684-8},
url = {https://pub.dzne.de/record/259245},
}