Impaired ATF3 signaling involves SNAP25 in SOD1 mutant ALS patients

Yazar V, Kühlwein JK, Knehr A, Grozdanov V, Ekici AB, Ludolph AC, Danzer KM (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 13

Article Number: 12019

Journal Issue: 1

DOI: 10.1038/s41598-023-38684-8

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 SOD1 G93A 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.

Authors with CRIS profile

Arif Bülent Ekici Lehrstuhl für Humangenetik

Involved external institutions

Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE)

How to cite

APA:

Yazar, V., Kühlwein, J.K., Knehr, A., Grozdanov, V., Ekici, A.B., Ludolph, A.C., & Danzer, K.M. (2023). Impaired ATF3 signaling involves SNAP25 in SOD1 mutant ALS patients. Scientific Reports, 13(1). https://doi.org/10.1038/s41598-023-38684-8

MLA:

Yazar, Volkan, et al. "Impaired ATF3 signaling involves SNAP25 in SOD1 mutant ALS patients." Scientific Reports 13.1 (2023).

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