TY  - JOUR
AU  - Rehbach, Kristina
AU  - Kesavan, Jaideep
AU  - Hauser, Stefan
AU  - Ritzenhofen, Swetlana
AU  - Jungverdorben, Johannes
AU  - Schüle, Rebecca
AU  - Schöls, Ludger
AU  - Peitz, Michael
AU  - Brüstle, Oliver
TI  - Multiparametric rapid screening of neuronal process pathology for drug target identification in HSP patient-specific neurons.
JO  - Scientific reports
VL  - 9
IS  - 1
SN  - 2045-2322
CY  - [London]
PB  - Macmillan Publishers Limited, part of Springer Nature
M1  - DZNE-2020-07109
SP  - 9615
PY  - 2019
AB  - 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
KW  - Biomarkers
KW  - Cell Differentiation
KW  - Cells, Cultured
KW  - Drug Discovery: methods
KW  - Drug Evaluation, Preclinical: methods
KW  - Haploinsufficiency
KW  - Humans
KW  - Induced Pluripotent Stem Cells: cytology
KW  - Induced Pluripotent Stem Cells: drug effects
KW  - Induced Pluripotent Stem Cells: metabolism
KW  - Neural Stem Cells: cytology
KW  - Neural Stem Cells: drug effects
KW  - Neural Stem Cells: metabolism
KW  - Neuronal Outgrowth
KW  - Neurons: drug effects
KW  - Neurons: metabolism
KW  - Phenotype
KW  - Spastic Paraplegia, Hereditary: drug therapy
KW  - Spastic Paraplegia, Hereditary: etiology
KW  - Spastic Paraplegia, Hereditary: metabolism
KW  - Spastin: genetics
LB  - PUB:(DE-HGF)16
C6  - pmid:31270336
C2  - pmc:PMC6610147
DO  - DOI:10.1038/s41598-019-45246-4
UR  - https://pub.dzne.de/record/140787
ER  -