References of "Schwamborn, Jens Christian 50003060"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailPINK1 deficiency impairs adult neurogenesis of dopaminergic neurons
Brown, Sarah J; Boussaad, Ibrahim UL; Jarazo, Javier UL et al

in Scientific Reports (2021)

Detailed reference viewed: 55 (0 UL)
Full Text
Peer Reviewed
See detailA human stem cell-derived test system for agents modifying neuronal N-methyl-d-aspartate-type glutamate receptor Ca2+-signalling
Klima, Stefanie; Brüll, Markus; Spreng, Anna-Sophie et al

in Archives of Toxicology (2021)

Detailed reference viewed: 21 (0 UL)
Full Text
Peer Reviewed
See detailMethod Optimization of Skin Biopsy-Derived Fibroblast Culture for Reprogramming Into Induced Pluripotent Stem Cells
Mommaerts, Kathleen; Bellora, Camille; Lambert, Pauline et al

in Biopreservation and Biobanking (2021)

Detailed reference viewed: 40 (0 UL)
Full Text
Peer Reviewed
See detailA robust protocol for the generation of human midbrain organoids
Zagare, Alise UL; Gobin, Matthieu UL; Monzel, Anna et al

in STAR Protocols (2021)

Detailed reference viewed: 64 (4 UL)
Full Text
Peer Reviewed
See detailMitochondrial and Clearance Impairment in p.D620N VPS35 Patient-Derived Neurons
Hanss, Zoé UL; Larsen, Simone UL; Antony, Paul UL et al

in Movement Disorders (2020)

Background: VPS35 is part of the retromer complex and is responsible for the trafficking and recycling of proteins implicated in autophagy and lysosomal degradation, but also takes part in the degradation ... [more ▼]

Background: VPS35 is part of the retromer complex and is responsible for the trafficking and recycling of proteins implicated in autophagy and lysosomal degradation, but also takes part in the degradation of mitochondrial proteins via mitochondria-derived vesicles. The p.D620N mutation of VPS35 causes an autosomal-dominant form of Parkinson’s disease (PD), clinically representing typical PD. Objective: Most of the studies on p.D620N VPS35 were performed on human tumor cell lines, rodent models overexpressing mutant VPS35, or in patient-derived fibroblasts. Here, based on identified target proteins, we investigated the implication of mutant VPS35 in autophagy, lysosomal degradation, and mitochondrial function in induced pluripotent stem cell-derived neurons from a patient harboring the p.D620N mutation. Methods: We reprogrammed fibroblasts from a PD patient carrying the p.D620N mutation in the VPS35 gene and from two healthy donors in induced pluripotent stem cells. These were subsequently differentiated into neuronal precursor cells to finally generate midbrain dopaminergic neurons. Results: We observed a decreased autophagic flux and lysosomal mass associated with an accumulation of α-synuclein in patient-derived neurons compared to controls. Moreover, patient-derived neurons presented a mitochondrial dysfunction with decreased membrane potential, impaired mitochondrial respiration, and increased production of reactive oxygen species associated with a defect in mitochondrial quality control via mitophagy. Conclusion: We describe for the first time the impact of the p.D620N VPS35 mutation on autophago-lysosome pathway and mitochondrial function in stem cell-derived neurons from an affected p.D620N carrier and define neuronal phenotypes for future pharmacological interventions [less ▲]

Detailed reference viewed: 63 (3 UL)
Full Text
Peer Reviewed
See detailGenetic Architecture of Parkinson's Disease in the Indian Population: Harnessing Genetic Diversity to Address Critical Gaps in Parkinson's Disease Research.
Rajan, Roopa; Divya, K. P.; Kandadai, Rukmini Mridula et al

in Frontiers in neurology (2020), 11

Over the past two decades, our understanding of Parkinson's disease (PD) has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability ... [more ▼]

Over the past two decades, our understanding of Parkinson's disease (PD) has been gleaned from the discoveries made in familial and/or sporadic forms of PD in the Caucasian population. The transferability and the clinical utility of genetic discoveries to other ethnically diverse populations are unknown. The Indian population has been under-represented in PD research. The Genetic Architecture of PD in India (GAP-India) project aims to develop one of the largest clinical/genomic bio-bank for PD in India. Specifically, GAP-India project aims to: (1) develop a pan-Indian deeply phenotyped clinical repository of Indian PD patients; (2) perform whole-genome sequencing in 500 PD samples to catalog Indian genetic variability and to develop an Indian PD map for the scientific community; (3) perform a genome-wide association study to identify novel loci for PD and (4) develop a user-friendly web-portal to disseminate results for the scientific community. Our "hub-spoke" model follows an integrative approach to develop a pan-Indian outreach to develop a comprehensive cohort for PD research in India. The alignment of standard operating procedures for recruiting patients and collecting biospecimens with international standards ensures harmonization of data/bio-specimen collection at the beginning and also ensures stringent quality control parameters for sample processing. Data sharing and protection policies follow the guidelines established by local and national authorities.We are currently in the recruitment phase targeting recruitment of 10,200 PD patients and 10,200 healthy volunteers by the end of 2020. GAP-India project after its completion will fill a critical gap that exists in PD research and will contribute a comprehensive genetic catalog of the Indian PD population to identify novel targets for PD. [less ▲]

Detailed reference viewed: 101 (4 UL)
Full Text
Peer Reviewed
See detailMachine learning-assisted neurotoxicity prediction in human midbrain organoids
Monzel, Anna Sophia UL; Hemmer, K; Smits, Lisa UL et al

in Parkinsonism and Related Disorders (2020)

Detailed reference viewed: 89 (14 UL)
Full Text
Peer Reviewed
See detailReduced astrocytic reactivity in human brains and midbrain organoids with PRKN mutations
Kano, Masayoshi; Takanashi, Masashi; Oyama, Genko et al

in NPJ Parkinson's Disease (2020)

Detailed reference viewed: 37 (1 UL)
Full Text
Peer Reviewed
See detailUsing High-Content Screening to Generate Single-Cell Gene-Corrected Patient-Derived iPS Clones Reveals Excess Alpha-Synuclein with Familial Parkinson's Disease Point Mutation A30P.
Barbuti, Peter UL; Antony, Paul UL; Rodrigues Santos, Bruno UL et al

in Cells (2020), 9(9),

The generation of isogenic induced pluripotent stem cell (iPSC) lines using CRISPR-Cas9 technology is a technically challenging, time-consuming process with variable efficiency. Here we use fluorescence ... [more ▼]

The generation of isogenic induced pluripotent stem cell (iPSC) lines using CRISPR-Cas9 technology is a technically challenging, time-consuming process with variable efficiency. Here we use fluorescence-activated cell sorting (FACS) to sort biallelic CRISPR-Cas9 edited single-cell iPSC clones into high-throughput 96-well microtiter plates. We used high-content screening (HCS) technology and generated an in-house developed algorithm to select the correctly edited isogenic clones for continued expansion and validation. In our model we have gene-corrected the iPSCs of a Parkinson's disease (PD) patient carrying the autosomal dominantly inherited heterozygous c.88G>C mutation in the SNCA gene, which leads to the pathogenic p.A30P form of the alpha-synuclein protein. Undertaking a PCR restriction-digest mediated clonal selection strategy prior to sequencing, we were able to post-sort validate each isogenic clone using a quadruple screening strategy prior to generating footprint-free isogenic iPSC lines, retaining a normal molecular karyotype, pluripotency and three germ-layer differentiation potential. Directed differentiation into midbrain dopaminergic neurons revealed that SNCA expression is reduced in the gene-corrected clones, which was validated by a reduction at the alpha-synuclein protein level. The generation of single-cell isogenic clones facilitates new insights in the role of alpha-synuclein in PD and furthermore is applicable across patient-derived disease models. [less ▲]

Detailed reference viewed: 108 (3 UL)
Full Text
Peer Reviewed
See detailA patient-based model of RNA mis-splicing uncovers treatment targets in Parkinson's disease.
Boussaad, Ibrahim UL; Obermaier, Carolin D.; Hanss, Zoé et al

in Science translational medicine (2020), 12(560),

Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder with monogenic forms representing prototypes of the underlying molecular pathology and reproducing to variable degrees the sporadic ... [more ▼]

Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder with monogenic forms representing prototypes of the underlying molecular pathology and reproducing to variable degrees the sporadic forms of the disease. Using a patient-based in vitro model of PARK7-linked PD, we identified a U1-dependent splicing defect causing a drastic reduction in DJ-1 protein and, consequently, mitochondrial dysfunction. Targeting defective exon skipping with genetically engineered U1-snRNA recovered DJ-1 protein expression in neuronal precursor cells and differentiated neurons. After prioritization of candidate drugs, we identified and validated a combinatorial treatment with the small-molecule compounds rectifier of aberrant splicing (RECTAS) and phenylbutyric acid, which restored DJ-1 protein and mitochondrial dysfunction in patient-derived fibroblasts as well as dopaminergic neuronal cell loss in mutant midbrain organoids. Our analysis of a large number of exomes revealed that U1 splice-site mutations were enriched in sporadic PD patients. Therefore, our study suggests an alternative strategy to restore cellular abnormalities in in vitro models of PD and provides a proof of concept for neuroprotection based on precision medicine strategies in PD. [less ▲]

Detailed reference viewed: 153 (8 UL)
Full Text
Peer Reviewed
See detailImpaired Mitochondrial-Endoplasmic Reticulum Interaction and Mitophagy in Miro1-Mutant Neurons in Parkinson’s Disease
Berenguer-Escuder, Clara; Grossmann, Dajana; Antony, Paul UL et al

in Human Molecular Genetics (2020)

Detailed reference viewed: 373 (27 UL)
Full Text
Peer Reviewed
See detailMidbrain organoids: A new tool to investigate Parkinson's disease
Smits, Lisa UL; Schwamborn, Jens Christian UL

in Frontiers in Cell and Developmental Biology (2020)

Detailed reference viewed: 123 (11 UL)
Full Text
Peer Reviewed
See detailEpitope imprinting of alpha-synuclein for sensing in Parkinson's brain organoid culture medium
Lee, Mei-Hwa; Thomas, James; Su, Zi-Lin et al

in Biosensors and Bioelectronics (2020)

Detailed reference viewed: 51 (0 UL)
Full Text
Peer Reviewed
See detailReproducible generation of human midbrain organoids for in vitro modeling of Parkinson’s disease
Nickels, Sarah Louise UL; Modamio Chamarro, Jennifer UL; Mendes-Pinheiro, Barbara et al

in Stem Cell Research (2020)

Detailed reference viewed: 107 (19 UL)
Full Text
Peer Reviewed
See detailSingle-cell transcriptomics reveals multiple neuronal cell types in human midbrain-specific organoids
Smits, Lisa UL; Magni, Stefano UL; Kinugawa, Kaoru et al

in Cell and Tissue Research (2020)

Detailed reference viewed: 89 (9 UL)