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Open AccessArticle

Human Spinal Motor Neurons Are Particularly Vulnerable to Cerebrospinal Fluid of Amyotrophic Lateral Sclerosis Patients

1
Department of Neurology, Technische Universität Dresden, 01307 Dresden, Germany
2
Department of Neurology, Städtisches Klinikum Dresden, 01129 Dresden, Germany
3
German Center for Neurodegenerative Diseases (DZNE), 01307 Dresden, Germany
4
Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307 Dresden, Germany
5
Translational Neurodegeneration Section “Albrecht-Kossel”, Department of Neurology, University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany
6
German Center for Neurodegenerative Diseases (DZNE) Rostock, 18147 Rostock, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(10), 3564; https://doi.org/10.3390/ijms21103564
Received: 12 March 2020 / Revised: 9 May 2020 / Accepted: 13 May 2020 / Published: 18 May 2020
(This article belongs to the Special Issue hiPSC-Derived Cells as Models for Drug Discovery)
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. View Full-Text
Keywords: amyotrophic lateral sclerosis; ALS; cerebrospinal fluid; Golgi fragmentation; superoxide dismutase 1; fused in sarcoma amyotrophic lateral sclerosis; ALS; cerebrospinal fluid; Golgi fragmentation; superoxide dismutase 1; fused in sarcoma
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MDPI and ACS Style

Bräuer, S.; Günther, R.; Sterneckert, J.; Glaß, H.; Hermann, A. Human Spinal Motor Neurons Are Particularly Vulnerable to Cerebrospinal Fluid of Amyotrophic Lateral Sclerosis Patients. Int. J. Mol. Sci. 2020, 21, 3564.

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