%0 Journal Article
%A Rehbach, Kristina
%A Kesavan, Jaideep
%A Hauser, Stefan
%A Ritzenhofen, Swetlana
%A Jungverdorben, Johannes
%A Schüle, Rebecca
%A Schöls, Ludger
%A Peitz, Michael
%A Brüstle, Oliver
%T Multiparametric rapid screening of neuronal process pathology for drug target identification in HSP patient-specific neurons.
%J Scientific reports
%V 9
%N 1
%@ 2045-2322
%C [London]
%I Macmillan Publishers Limited, part of Springer Nature
%M DZNE-2020-07109
%P 9615
%D 2019
%X Axonal degeneration is a key pathology of neurodegenerative diseases, including hereditary spastic paraplegia (HSP), a disorder characterized by spasticity in the lower limbs. Treatments for HSP and other neurodegenerative diseases are mainly symptomatic. While iPSC-derived neurons are valuable for drug discovery and target identification, these applications require robust differentiation paradigms and rapid phenotypic read-outs ranging between hours and a few days. Using spastic paraplegia type 4 (SPG4, the most frequent HSP subtype) as an exemplar, we here present three rapid phenotypic assays for uncovering neuronal process pathologies in iPSC-derived glutamatergic cortical neurons. Specifically, these assays detected a 51
%K Biomarkers
%K Cell Differentiation
%K Cells, Cultured
%K Drug Discovery: methods
%K Drug Evaluation, Preclinical: methods
%K Haploinsufficiency
%K Humans
%K Induced Pluripotent Stem Cells: cytology
%K Induced Pluripotent Stem Cells: drug effects
%K Induced Pluripotent Stem Cells: metabolism
%K Neural Stem Cells: cytology
%K Neural Stem Cells: drug effects
%K Neural Stem Cells: metabolism
%K Neuronal Outgrowth
%K Neurons: drug effects
%K Neurons: metabolism
%K Phenotype
%K Spastic Paraplegia, Hereditary: drug therapy
%K Spastic Paraplegia, Hereditary: etiology
%K Spastic Paraplegia, Hereditary: metabolism
%K Spastin: genetics
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:31270336
%2 pmc:PMC6610147
%R 10.1038/s41598-019-45246-4
%U https://pub.dzne.de/record/140787