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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

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.

Details

Original languageEnglish
Article number3564
JournalInternational journal of molecular sciences
Volume21
Issue number10
Publication statusPublished - 2 May 2020
Peer-reviewedYes

External IDs

PubMed 32443559
ORCID /0000-0002-7688-3124/work/142250017
PubMedCentral PMC7278966

Keywords

Sustainable Development Goals

Keywords

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

Library keywords