Human spinal motor neurons are particularly vulnerable to cerebrospinal fluid of amyotrophic lateral sclerosis patients

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung


  • Stefan Bräuer - , Technische Universität Dresden (Autor:in)
  • René Günther - , Technische Universität Dresden, Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE) (Autor:in)
  • Jared Sterneckert - , Center for Regenerative Therapies Dresden (CRTD) (Autor:in)
  • Hannes Glaß - , Universität Rostock (Autor:in)
  • Andreas Hermann - , Technische Universität Dresden, Universität Rostock, Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE) (Autor:in)


Amyotrophic lateral sclerosis (ALS) is the most common and devastating motor neuron (MN) disease. Its pathophysiological cascade is still enigmatic. More than 90% of ALS patients suffer from sporadic ALS, which makes it specifically demanding to generate appropriate model systems. One interesting aspect considering the seeding, spreading and further disease development of ALS is the cerebrospinal fluid (CSF). We therefore asked whether CSF from sporadic ALS patients is capable of causing disease typical changes in human patient-derived spinal MN cultures and thus could represent a novel model system for sporadic ALS. By using induced pluripotent stem cell (iPSC)-derived MNs from healthy controls and monogenetic forms of ALS we could demonstrate a harmful effect of ALS-CSF on healthy donor-derived human MNs. Golgi fragmentation—a typical finding in lower organism models and human postmortem tissue—was induced solely by addition of ALS-CSF, but not control-CSF. No other neurodegenerative hallmarks—including pathological protein aggregation—were found, underpinning Golgi fragmentation as early event in the neurodegenerative cascade. Of note, these changes occurred predominantly in MNs, the cell type primarily affected in ALS. We thus present a novel way to model early features of sporadic ALS.


FachzeitschriftInternational journal of molecular sciences
PublikationsstatusVeröffentlicht - 2 Mai 2020

Externe IDs

PubMed 32443559
ORCID /0000-0002-7688-3124/work/142250017


Ziele für nachhaltige Entwicklung


  • ALS, Amyotrophic lateral sclerosis, Cerebrospinal fluid, Fused in sarcoma, Golgi fragmentation, Superoxide dismutase 1