Combined dendritic and axonal deterioration are responsible for motoneuronopathy in patient-derived neuronal cell models of chorea-acanthocytosis

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung


  • Hannes Glaß - , University of Rostock (Autor:in)
  • Patrick Neumann - , Technische Universität Dresden (Autor:in)
  • Arun Pal - , Technische Universität Dresden (Autor:in)
  • Peter Reinhardt - , Technische Universität Dresden, AbbVie (Autor:in)
  • Alexander Storch - , University of Rostock, German Center for Neurodegenerative Diseases (Autor:in)
  • Jared Sterneckert - , IPS Zellen und neurodegenerative Erkrankungen (NFoG) (Autor:in)
  • Andreas Hermann - , University of Rostock, Technische Universität Dresden, German Center for Neurodegenerative Diseases (Autor:in)


Chorea acanthocytosis (ChAc), an ultra-rare devastating neurodegenerative disease, is caused by mutations in the VPS13A gene, which encodes for the protein chorein. Affected patients suffer from chorea, orofacial dyskinesia, epilepsy, parkinsonism as well as peripheral neuropathy. Although medium spinal neurons of the striatum are mainly affected, other regions are impaired as well over the course of the disease. Animal studies as well as studies on human erythrocytes suggest Lyn-kinase inhibition as valuable novel opportunity to treat ChAc. In order to investigate the peripheral neuropathy aspect, we analyzed induced pluripotent stem cell derived midbrain/hindbrain cell cultures from ChAc patients in vitro. We observed dendritic microtubule fragmentation. Furthermore, by using in vitro live cell imaging, we found a reduction in the number of lysosomes and mitochondria, shortened mitochondria, an increase in retrograde transport and hyperpolarization as measured with the fluorescent probe JC-1. Deep phenotyping pointed towards a proximal axonal deterioration as the primary axonal disease phenotype. Interestingly, pharmacological interventions, which proved to be successful in different models of ChAc, were ineffective in treating the observed axonal phenotypes. Our data suggests that treatment of this multifaceted disease might be cell type and/or neuronal subtype specific, and thus necessitates precision medicine in this ultra-rare disease.


FachzeitschriftInternational journal of molecular sciences
PublikationsstatusVeröffentlicht - 1 März 2020

Externe IDs

PubMed 32151030


Ziele für nachhaltige Entwicklung


  • Chorea Acanthocytosis (ChAc), Human induced pluripotent stem cells (iPSC), Lysosomes, Microfluidic chambers (MFCs), Mitochondria, Motoneurons (MN), Organelle trafficking