% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Dash:281506,
      author       = {Dash, Banaja and Hermann, Andreas},
      title        = {{T}ranscriptomic {A}lteration in {FUS}-{ALS} {P}oints
                      {T}owards {A}poptosis-{R}ather than {F}erroptosis-{R}elated
                      {C}ell {D}eath {P}athway.},
      journal      = {Cells},
      volume       = {14},
      number       = {18},
      issn         = {2073-4409},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DZNE-2025-01127},
      pages        = {1417},
      year         = {2025},
      abstract     = {Amyotrophic lateral sclerosis (ALS) is a fatal type of
                      neurodegenerative disease marked by progressive and
                      selective degeneration of motor neurons (MNs) present in the
                      spinal cord, brain stem and motor cortex. However, the
                      intricate molecular mechanisms underlying primary cell death
                      pathways, including ferroptosis-related genes (FRGs)
                      mediating MN dysfunction in ALS, remain elusive.
                      Ferroptosis, a novel type of iron-dependent cell death with
                      the accumulation of lipid peroxidation products, stands
                      distinct from apoptotic-related stress and other cell death
                      mechanisms. Although growing advances have highlighted the
                      role of iron deposition, apoptosis and alteration of
                      antioxidant systems in ALS pathogenesis, there is little
                      data at the systems biology level. Therefore, we performed a
                      comprehensive bioinformatic analysis of bulk RNA-sequencing
                      (RNA-seq) data by systematically comparing the gene
                      expression profiles from iPSC-derived MNs of ALS patients
                      and healthy controls using our datasets as well as from the
                      GEO database to reveal the role of ferroptosis-related gene
                      alterations in ALS, especially in selective MN vulnerability
                      of FUSED IN SARCOMA (FUS) mutations. In this study, we first
                      identified differentially expressed genes (DEGs) between FUS
                      mutant and healthy controls. Subsequently, the crossover
                      genes between DEGs and FRGs were selected as differentially
                      expressed ferroptosis-related genes (DEFRGs). Functional
                      enrichment and protein-protein interaction (PPI) analysis of
                      DEFRGs identified that DNA damage, stress response and extra
                      cellular matrix (ECM) were the most significantly
                      dysregulated functions/pathways in FUS-ALS causing mutations
                      compared to healthy controls. While GSEA analysis showed
                      enrichment of genes associated with apoptosis, the degree of
                      ferroptosis and iron ion homeostasis/response to iron of FUS
                      MNs was lower. Altogether, our findings may contribute to a
                      better understanding of the relevant role of cell death
                      pathways underlying selective vulnerability of MNs to
                      neurodegeneration in FUS-ALS pathophysiology.},
      keywords     = {Ferroptosis: genetics / Humans / Amyotrophic Lateral
                      Sclerosis: genetics / Amyotrophic Lateral Sclerosis:
                      pathology / Apoptosis: genetics / RNA-Binding Protein FUS:
                      genetics / RNA-Binding Protein FUS: metabolism /
                      Transcriptome: genetics / Motor Neurons: metabolism / Motor
                      Neurons: pathology / Induced Pluripotent Stem Cells:
                      metabolism / Gene Expression Profiling / ALS (Other) /
                      RNA-sequencing (Other) / apoptosis (Other) / differentially
                      expressed genes (Other) / ferroptosis (Other) /
                      ferroptosis-related genes (Other) / gene expression omnibus
                      (Other) / iPSC (Other) / motor neuron (Other) / RNA-Binding
                      Protein FUS (NLM Chemicals) / FUS protein, human (NLM
                      Chemicals)},
      cin          = {AG Hermann},
      ddc          = {570},
      cid          = {I:(DE-2719)1511100},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41002383},
      pmc          = {pmc:PMC12468769},
      doi          = {10.3390/cells14181417},
      url          = {https://pub.dzne.de/record/281506},
}