2020
DOI: 10.3390/ijms21051797
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Combined Dendritic and Axonal Deterioration Are Responsible for Motoneuronopathy in Patient-Derived Neuronal Cell Models of Chorea-Acanthocytosis

Abstract: 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 … Show more

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Cited by 14 publications
(12 citation statements)
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“…All iPSC lines were matured to spinal MNs in microfluidic chambers (MFCs), in which only axons could reach and fully penetrate the microgroove barrier of channels from the proximal soma seeding site to distal exits ( Naumann et al, 2018 ) ( Fig 1A ), thereby enabling axon-specific studies with defined antero- versus retrograde orientation. Of note, our differentiation protocol combined with 900 μm length of microgrooves resulted in exclusive penetration by MN axons, as we documented previously ( Pal et al, 2018 ; Glaβ et al, 2020 ). We performed fast dual-color live imaging of mitochondria and lysosomes at strictly standardized distal versus proximal readout positions as described ( Naumann et al, 2018 ) on day D21.…”
Section: Resultssupporting
confidence: 70%
See 1 more Smart Citation
“…All iPSC lines were matured to spinal MNs in microfluidic chambers (MFCs), in which only axons could reach and fully penetrate the microgroove barrier of channels from the proximal soma seeding site to distal exits ( Naumann et al, 2018 ) ( Fig 1A ), thereby enabling axon-specific studies with defined antero- versus retrograde orientation. Of note, our differentiation protocol combined with 900 μm length of microgrooves resulted in exclusive penetration by MN axons, as we documented previously ( Pal et al, 2018 ; Glaβ et al, 2020 ). We performed fast dual-color live imaging of mitochondria and lysosomes at strictly standardized distal versus proximal readout positions as described ( Naumann et al, 2018 ) on day D21.…”
Section: Resultssupporting
confidence: 70%
“…The cultures were devoid of glia cells and astrocytes. Neurites penetrating the microchannels and sprouting out at the distal exit are virtually 100% axon-pure ( Glaβ et al, 2020 ).…”
Section: Methodsmentioning
confidence: 99%
“…We performed the analysis as previously described by Glaß et al [50]. After imaging a neuron or neuronal network, we converted the picture into a 2-bit image using the "threshold" function from Fiji (ImageJ-win64, open source).…”
Section: Analysis Of Neuronal Network Degenerationmentioning
confidence: 99%
“…The main neuropathologic feature in VPS13A disease is a selective degeneration of the caudate and putamen nuclei [ 4 , 5 , 6 ], due to massive cell death of medium spiny neurons (MSNs) and striatal interneurons [ 7 , 8 ]. Moreover, many other neuronal subtypes, such as dopaminergic neurons or motoneurons, are affected as well, contributing to the explanation of a plethora of pathological symptoms that include chorea, dystonia, involuntary oral biting, and orofacial dyskinesia, among others [ 9 ].…”
Section: Introductionmentioning
confidence: 99%