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@ARTICLE{Lehmann:271071,
      author       = {Lehmann, Johannes and Aly, Amr and Steffke, Christina and
                      Fabbio, Luca and Mayer, Valentin and Dikwella, Natalie and
                      Halablab, Kareen and Roselli, Francesco and Seiffert, Simone
                      and Boeckers, Tobias M and Brenner, David and Kabashi, Edor
                      and Mulaw, Medhanie and Ho, Ritchie and Catanese, Alberto},
      title        = {{H}eterozygous knockout of {S}ynaptotagmin13 phenocopies
                      {ALS} features and {TP}53 activation in human motor
                      neurons.},
      journal      = {Cell death $\&$ disease},
      volume       = {15},
      number       = {8},
      issn         = {2041-4889},
      address      = {London [u.a.]},
      publisher    = {Nature Publishing Group},
      reportid     = {DZNE-2024-00943},
      pages        = {560},
      year         = {2024},
      abstract     = {Spinal motor neurons (MNs) represent a highly vulnerable
                      cellular population, which is affected in fatal
                      neurodegenerative diseases such as amyotrophic lateral
                      sclerosis (ALS) and spinal muscular atrophy (SMA). In this
                      study, we show that the heterozygous loss of SYT13 is
                      sufficient to trigger a neurodegenerative phenotype
                      resembling those observed in ALS and SMA. SYT13+/-
                      hiPSC-derived MNs displayed a progressive manifestation of
                      typical neurodegenerative hallmarks such as loss of synaptic
                      contacts and accumulation of aberrant aggregates. Moreover,
                      analysis of the SYT13+/- transcriptome revealed a
                      significant impairment in biological mechanisms involved in
                      motoneuron specification and spinal cord differentiation.
                      This transcriptional portrait also strikingly correlated
                      with ALS signatures, displaying a significant convergence
                      toward the expression of pro-apoptotic and pro-inflammatory
                      genes, which are controlled by the transcription factor
                      TP53. Our data show for the first time that the heterozygous
                      loss of a single member of the synaptotagmin family, SYT13,
                      is sufficient to trigger a series of abnormal alterations
                      leading to MN sufferance, thus revealing novel insights into
                      the selective vulnerability of this cell population.},
      keywords     = {Humans / Tumor Suppressor Protein p53: metabolism / Tumor
                      Suppressor Protein p53: genetics / Motor Neurons: metabolism
                      / Motor Neurons: pathology / Synaptotagmins: metabolism /
                      Synaptotagmins: genetics / Amyotrophic Lateral Sclerosis:
                      genetics / Amyotrophic Lateral Sclerosis: metabolism /
                      Amyotrophic Lateral Sclerosis: pathology / Heterozygote /
                      Phenotype / Induced Pluripotent Stem Cells: metabolism /
                      Induced Pluripotent Stem Cells: pathology / Cell
                      Differentiation: genetics / Gene Knockout Techniques / Tumor
                      Suppressor Protein p53 (NLM Chemicals) / Synaptotagmins (NLM
                      Chemicals) / TP53 protein, human (NLM Chemicals)},
      cin          = {AG Böckers / AG Roselli / Clinical Study Center Ulm ;
                      Clinical Study Center (Ulm)},
      ddc          = {570},
      cid          = {I:(DE-2719)1910002 / I:(DE-2719)1910001 /
                      I:(DE-2719)5000077},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 352 -
                      Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39097602},
      pmc          = {pmc:PMC11297993},
      doi          = {10.1038/s41419-024-06957-3},
      url          = {https://pub.dzne.de/record/271071},
}