% 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{Hartmann:282297,
      author       = {Hartmann, Christiane and Haß, Christina and Knobloch,
                      Muriel and Barrantes, Israel and Fumagalli, Laura and
                      Premereur, Jessie and Markert, Franz and Peters, Maite and
                      Koromila, Georgia and Hartmann, Alexander and Jäger,
                      Kathrin and Abel, Jette and Mancuso, Renzo and Storch,
                      Alexander and Walter, Michael and Fuellen, Georg and
                      Hermann, Andreas},
      title        = {{P}rematurely {A}ged {H}uman {M}icroglia {E}xhibit
                      {I}mpaired {S}tress {R}esponse and {D}efective
                      {N}ucleocytoplasmic {S}huttling of {ALS} {A}ssociated
                      {FUS}.},
      journal      = {Aging cell},
      volume       = {24},
      number       = {11},
      issn         = {1474-9718},
      address      = {Oxford [u.a.]},
      publisher    = {Wiley-Blackwell},
      reportid     = {DZNE-2025-01267},
      pages        = {e70232},
      year         = {2025},
      abstract     = {Microglia, the brain's resident immune cells, are crucial
                      for maintaining healthy brain homeostasis. However, as the
                      brain ages, microglia can shift from a neuroprotective to a
                      neurotoxic phenotype, contributing to chronic inflammation
                      and promoting neurodegenerative processes. Despite the
                      importance of understanding microglial aging, there are
                      currently few human in vitro models to study these
                      processes. To address this gap, we have developed a model in
                      which human microglia undergo accelerated aging through
                      inducible progerin expression. HMC3-Progerin cells display
                      key age-related markers such as activation of the
                      senescence-associated secretory phenotype (SASP) as well as
                      an increase in DNA damage. These prematurely aged HMC3 cells
                      show a reduced response to LPS activation, exhibit
                      impairments in essential microglial functions including
                      decreased migration and phagocytosis as well as
                      transcriptomic alterations including a shift observed in
                      aging and neurodegeneration. Additionally, we observed an
                      impaired stress response and a defect in nucleocytoplasmic
                      transport, especially affecting the amyotrophic lateral
                      sclerosis (ALS) associated protein FUS. This suggests that
                      microglia play a contributory role in driving
                      neurodegenerative processes in the aging brain. Our
                      microglia aging model offers a valuable tool for exploring
                      how aged microglia affect brain function, enhancing our
                      understanding of their role in brain aging.},
      keywords     = {Humans / Microglia: metabolism / Microglia: pathology /
                      Amyotrophic Lateral Sclerosis: metabolism / Amyotrophic
                      Lateral Sclerosis: pathology / Amyotrophic Lateral
                      Sclerosis: genetics / RNA-Binding Protein FUS: metabolism /
                      Cellular Senescence / Active Transport, Cell Nucleus /
                      Stress, Physiological / Phagocytosis / FUS (Other) / aging
                      (Other) / aging clock (Other) / amyotrophic lateral
                      sclerosis (Other) / microglia (Other) / nucleocytoplasmic
                      shuttling (Other) / progerin (Other) / senolytics (Other) /
                      RNA-Binding Protein FUS (NLM Chemicals)},
      cin          = {AG Hermann / AG Storch},
      ddc          = {610},
      cid          = {I:(DE-2719)1511100 / I:(DE-2719)5000014},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40970514},
      pmc          = {pmc:PMC12610945},
      doi          = {10.1111/acel.70232},
      url          = {https://pub.dzne.de/record/282297},
}