LIVIVO - Search results -

Search results

Result 1 - 8 of total 8

Search options

Article ; Online: An iPSC model for POLR3A-associated spastic ataxia: Generation of three unrelated patient cell lines.

Manibarathi, Kalaivani / Pham, Tam / Hengel, Holger / Synofzik, Matthis / Nagel, Maike / Schüle, Rebecca

2024 Volume 76, Page(s) 103363

Abstract: Spastic Ataxias (SA) are a group of neurodegenerative disorders with combined pyramidal and cerebellar system affection, leading to an overlap phenotype between Hereditary Spastic Paraplegias (HSP) and Cerebellar Ataxias (CA). Here we describe the ... ...

Abstract	Spastic Ataxias (SA) are a group of neurodegenerative disorders with combined pyramidal and cerebellar system affection, leading to an overlap phenotype between Hereditary Spastic Paraplegias (HSP) and Cerebellar Ataxias (CA). Here we describe the generation of iPSCs from three unrelated patients with an ultra-rare subtype of SA caused by compound heterozygous mutations in POLR3A, that encodes the largest subunit of RNA polymerase III. iPSCs were reprogrammed from normal human dermal fibroblasts (NHDFs) using episomal reprogramming with integration-free plasmid vectors: HIHRSi004-A, derived from a 44 year-old male carrying the mutations c.1909 + 22G > A/c.3944_3945delTG, HIHRSi005-A obtained from a 66 year-old male carrying the mutations c.1909 + 22G > A/c.1531C > T, and HIHRSi006-A from a 27 year-old male carrying the mutations c.1909 + 22G > A/c.2472_2472delC (ENST00000372371.8).
MeSH term(s)	Adult ; Aged ; Humans ; Male ; Cell Line ; Induced Pluripotent Stem Cells/metabolism ; Intellectual Disability ; Muscle Spasticity/genetics ; Mutation ; Optic Atrophy ; RNA Polymerase III/genetics ; RNA Polymerase III/metabolism ; Spinocerebellar Ataxias/genetics
Chemical Substances	POLR3A protein, human (EC 2.7.7.6) ; RNA Polymerase III (EC 2.7.7.6)
Language	English
Publishing date	2024-02-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2393143-7
ISSN	1876-7753 ; 1873-5061
ISSN (online)	1876-7753
ISSN	1873-5061
DOI	10.1016/j.scr.2024.103363
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article: Unraveling Axonal Transcriptional Landscapes: Insights from iPSC-Derived Cortical Neurons and Implications for Motor Neuron Degeneration.

Xu, Jishu / Hörner, Michaela / Nagel, Maike / Korneck, Milena / Noß, Marvin / Hauser, Stefan / Schöls, Ludger / Admard, Jakob / Casadei, Nicolas / Schüle, Rebecca

bioRxiv : the preprint server for biology

2024

Abstract: Neuronal function and pathology are deeply influenced by the distinct molecular profiles of the axon and soma. Traditional studies have often overlooked these differences due to the technical challenges of compartment specific analysis. In this study, we ...

Abstract	Neuronal function and pathology are deeply influenced by the distinct molecular profiles of the axon and soma. Traditional studies have often overlooked these differences due to the technical challenges of compartment specific analysis. In this study, we employ a robust RNA-sequencing (RNA-seq) approach, using microfluidic devices, to generate high-quality axonal transcriptomes from iPSC-derived cortical neurons (CNs). We achieve high specificity of axonal fractions, ensuring sample purity without contamination. Comparative analysis revealed a unique and specific transcriptional landscape in axonal compartments, characterized by diverse transcript types, including protein-coding mRNAs, ribosomal proteins (RPs), mitochondrial-encoded RNAs, and long non-coding RNAs (lncRNAs). Previous works have reported the existence of transcription factors (TFs) in the axon. Here, we detect a subset of previously unreported TFs specific to the axon and indicative of their active participation in transcriptional regulation. To investigate transcripts and pathways essential for central motor neuron (MN) degeneration and maintenance we analyzed
Language	English
Publishing date	2024-03-29
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.26.586780
Database	MEDical Literature Analysis and Retrieval System OnLINE

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Article ; Online: The kinesin motor KIF1C is a putative transporter of the exon junction complex in neuronal cells.

Nagel, Maike / Noss, Marvin / Xu, Jishu / Horn, Nicola / Ueffing, Marius / Boldt, Karsten / Schuele, Rebecca

RNA (New York, N.Y.)

2022

Abstract: Neurons critically depend on regulated RNA localization and tight control of spatio-temporal gene expression to maintain their morphological and functional integrity. Mutations in the kinesin motor protein gene KIF1C cause Hereditary Spastic Paraplegia, ... ...

Abstract	Neurons critically depend on regulated RNA localization and tight control of spatio-temporal gene expression to maintain their morphological and functional integrity. Mutations in the kinesin motor protein gene KIF1C cause Hereditary Spastic Paraplegia, an autosomal recessive disease leading to predominant degeneration of the long axons of central motoneurons. In this study we aimed to gain insight into the molecular function of KIF1C and understand how KIF1C dysfunction contributes to motoneuron degeneration. We used affinity proteomics in neuronally differentiated neuroblastoma cells (SH-SY5Y) to identify the protein complex associated with KIF1C in neuronal cells; candidate interactions were then validated by immunoprecipitation and mislocalization of putative KIF1C cargoes was studied by immunostainings. We found KIF1C to interact with all core components of the exon junction complex (EJC); expression of mutant KIF1C in neuronal cells leads to loss of the typical localization distally in neurites. Instead, EJC core components accumulate in the pericentrosomal region, here co-localizing with mutant KIF1C. These findings suggest KIF1C as a neuronal transporter of the EJC. Interestingly, the binding of KIF1C to the EJC is RNA-mediated, as treatment with RNAse prior to immunoprecipitation almost completely abolishes the interaction. Silica-based solid-phase extraction of UV-crosslinked RNA-protein complexes furthermore supports direct interaction of KIF1C with RNA, as recently also demonstrated for kinesin heavy chain. Taken together, our findings are consistent with a model where KIF1C transports mRNA in an EJC-bound and therefore transcriptionally silenced state along neurites, thus providing the missing link between the EJC and mRNA localization in neurons.
Language	English
Publishing date	2022-10-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	1241540-6
ISSN	1469-9001 ; 1355-8382
ISSN (online)	1469-9001
ISSN	1355-8382
DOI	10.1261/rna.079426.122
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4777: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Generation of the CRISPR/Cas9-mediated KIF1C knock-out human iPSC line HIHRSi003-A-1.

Nagel, Maike / Müßig, Sandra / Höflinger, Philip / Schöls, Ludger / Hauser, Stefan / Schüle, Rebecca

Stem cell research

2020 Volume 49, Page(s) 102059

Abstract: Bi-allelic loss-of-function mutations in the gene encoding the motor protein KIF1C are associated with Hereditary Spastic Paraplegia (HSP) type SPG58, a slowly progressive neurodegenerative motoneuron disease. The biological role of KIF1C is incompletely ...

Abstract	Bi-allelic loss-of-function mutations in the gene encoding the motor protein KIF1C are associated with Hereditary Spastic Paraplegia (HSP) type SPG58, a slowly progressive neurodegenerative motoneuron disease. The biological role of KIF1C is incompletely understood. We used a protein-based CRISPR/Cas9 genome editing approach to generate a homozygous KIF1C knock-out iPSC line (HIHRSi003-A-1) from a healthy control. This iPSC-KIF1C
MeSH term(s)	CRISPR-Cas Systems/genetics ; Gene Editing ; Homozygote ; Humans ; Induced Pluripotent Stem Cells ; Kinesin/genetics ; Spastic Paraplegia, Hereditary/genetics
Chemical Substances	KIF1C protein, human ; Kinesin (EC 3.6.4.4)
Language	English
Publishing date	2020-10-29
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1876-7753
ISSN (online)	1876-7753
DOI	10.1016/j.scr.2020.102059
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Generation of two iPSC lines derived from two unrelated patients with Gaucher disease.

Nagel, Maike / Reichbauer, Jennifer / Böhringer, Judith / Schelling, Yvonne / Krägeloh-Mann, Inge / Schüle, Rebecca / Ulmer, Ulrike

Stem cell research

2018 Volume 35, Page(s) 101336

Abstract: Gaucher disease is the most common autosomal recessive lysosomal storage disorder, caused by mutations in the β-glucocerebrosidase gene GBA. Here we describe generation of iPSC from skin-derived fibroblasts from two unrelated individuals with ... ...

Abstract	Gaucher disease is the most common autosomal recessive lysosomal storage disorder, caused by mutations in the β-glucocerebrosidase gene GBA. Here we describe generation of iPSC from skin-derived fibroblasts from two unrelated individuals with neuronopathic forms of Gaucher disease. The donor for line iPSC-GBA-1, a 21 month old girl, carried the recurring GBA mutation c.1448 T > C, p.Leu483Pro at homozygous state; fibroblasts for line iPS-GBA-2 were obtained from a 4 year old girl compound heterozygous for the GBA mutations c.667 T > C, p.Trp223Arg and c.1226A > G, p.Asn409Ser. iPSCs were developed using integration free episomal vectors (OCT4, KLF4; L-MYC, SOX2 (OSKM) and LIN28). Resource table.
MeSH term(s)	Alleles ; Cell Line ; Child, Preschool ; Female ; Gaucher Disease/genetics ; Gaucher Disease/metabolism ; Gaucher Disease/pathology ; Glucosylceramidase/metabolism ; Homozygote ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Induced Pluripotent Stem Cells/pathology ; Infant ; Mutation
Chemical Substances	Glucosylceramidase (EC 3.2.1.45)
Language	English
Publishing date	2018-11-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1876-7753
ISSN (online)	1876-7753
DOI	10.1016/j.scr.2018.10.021
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Calpastatin ablation aggravates the molecular phenotype in cell and animal models of Huntington disease.

Weber, Jonasz Jeremiasz / Kloock, Simon Johannes / Nagel, Maike / Ortiz-Rios, Midea Malena / Hofmann, Julian / Riess, Olaf / Nguyen, Huu Phuc

Neuropharmacology

2018 Volume 133, Page(s) 94–106

Abstract: Deciphering the molecular pathology of Huntington disease is of particular importance, not only for a better understanding of this neurodegenerative disease, but also to identify potential therapeutic targets. The polyglutamine-expanded disease protein ... ...

Abstract	Deciphering the molecular pathology of Huntington disease is of particular importance, not only for a better understanding of this neurodegenerative disease, but also to identify potential therapeutic targets. The polyglutamine-expanded disease protein huntingtin was shown to undergo proteolysis, which results in the accumulation of toxic and aggregation-prone fragments. Amongst several classes of proteolytic enzymes responsible for huntingtin processing, the group of calcium-activated calpains has been found to be a significant mediator of the disease protein toxicity. To confirm the impact of calpain-mediated huntingtin cleavage in Huntington disease, we analysed the effect of depleting or overexpressing the endogenous calpain inhibitor calpastatin in HEK293T cells transfected with wild-type or polyglutamine-expanded huntingtin. Moreover, we crossbred huntingtin knock-in mice with calpastatin knockout animals to assess its effect not only on huntingtin cleavage and aggregation but also additional molecular markers. We demonstrated that a reduced or ablated expression of calpastatin triggers calpain overactivation and a consequently increased mutant huntingtin cleavage in cells and in vivo. These alterations were accompanied by an elevated formation of predominantly cytoplasmic huntingtin aggregates. On the other hand, overexpression of calpastatin in cells attenuated huntingtin fragmentation and aggregation. In addition, we observed an enhanced cleavage of DARPP-32, p35 and synapsin-1 in neuronal tissue upon calpain overactivation. Our results corroborate the important role of calpains in the molecular pathogenesis of Huntington disease and endorse targeting these proteolytic enzymes as a therapeutic approach.
MeSH term(s)	Analysis of Variance ; Animals ; Autophagy/drug effects ; Autophagy/genetics ; Calpain/genetics ; Calpain/metabolism ; Cytoskeletal Proteins/deficiency ; Cytoskeletal Proteins/genetics ; Disease Models, Animal ; Dopamine and cAMP-Regulated Phosphoprotein 32/metabolism ; Gene Expression Regulation/genetics ; Glycoproteins/pharmacology ; HEK293 Cells ; Humans ; Huntington Disease/genetics ; Huntington Disease/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Synapsins/metabolism ; Transfection
Chemical Substances	Cytoskeletal Proteins ; Dopamine and cAMP-Regulated Phosphoprotein 32 ; Erc2 protein, mouse ; Glycoproteins ; Htt protein, mouse ; Nerve Tissue Proteins ; Nuclear Proteins ; Ppp1r1b protein, mouse ; RNA, Small Interfering ; Synapsins ; calpain inhibitors ; Calpain (EC 3.4.22.-)
Language	English
Publishing date	2018-01-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2018.01.022
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Ui I Zs.242: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: A combinatorial approach to identify calpain cleavage sites in the Machado-Joseph disease protein ataxin-3.

Weber, Jonasz J / Golla, Matthias / Guaitoli, Giambattista / Wanichawan, Pimthanya / Hayer, Stefanie N / Hauser, Stefan / Krahl, Ann-Christin / Nagel, Maike / Samer, Sebastian / Aronica, Eleonora / Carlson, Cathrine R / Schöls, Ludger / Riess, Olaf / Gloeckner, Christian J / Nguyen, Huu P / Hübener-Schmid, Jeannette

Brain : a journal of neurology

2017 Volume 140, Issue 5, Page(s) 1280–1299

Abstract: Ataxin-3, the disease protein in Machado-Joseph disease, is known to be proteolytically modified by various enzymes including two major families of proteases, caspases and calpains. This processing results in the generation of toxic fragments of the ... ...

Abstract	Ataxin-3, the disease protein in Machado-Joseph disease, is known to be proteolytically modified by various enzymes including two major families of proteases, caspases and calpains. This processing results in the generation of toxic fragments of the polyglutamine-expanded protein. Although various approaches were undertaken to identify cleavage sites within ataxin-3 and to evaluate the impact of fragments on the molecular pathogenesis of Machado-Joseph disease, calpain-mediated cleavage of the disease protein and the localization of cleavage sites remained unclear. Here, we report on the first precise localization of calpain cleavage sites in ataxin-3 and on the characterization of the resulting breakdown products. After confirming the occurrence of calpain-derived fragmentation of ataxin-3 in patient-derived cell lines and post-mortem brain tissue, we combined in silico prediction tools, western blot analysis, mass spectrometry, and peptide overlay assays to identify calpain cleavage sites. We found that ataxin-3 is primarily cleaved at two sites, namely at amino acid positions D208 and S256 and mutating amino acids at both cleavage sites to tryptophan nearly abolished ataxin-3 fragmentation. Furthermore, analysis of calpain cleavage-derived fragments showed distinct aggregation propensities and toxicities of C-terminal polyglutamine-containing breakdown products. Our data elucidate the important role of ataxin-3 proteolysis in the pathogenesis of Machado-Joseph disease and further emphasize the relevance of targeting this disease pathway as a treatment strategy in neurodegenerative disorders.
MeSH term(s)	Ataxin-3/metabolism ; Brain/metabolism ; Calpain/metabolism ; Cells, Cultured ; Combinatorial Chemistry Techniques ; Computer Simulation ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Machado-Joseph Disease/metabolism ; Peptide Hydrolases/metabolism ; Protein Aggregation, Pathological/metabolism ; Transfection
Chemical Substances	Peptide Hydrolases (EC 3.4.-) ; Ataxin-3 (EC 3.4.19.12) ; Calpain (EC 3.4.22.-)
Language	English
Publishing date	2017-05-01
Publishing country	England
Document type	Journal Article
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awx039
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui II Zs.26: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Bi-allelic variants in RNF170 are associated with hereditary spastic paraplegia.

Wagner, Matias / Osborn, Daniel P S / Gehweiler, Ina / Nagel, Maike / Ulmer, Ulrike / Bakhtiari, Somayeh / Amouri, Rim / Boostani, Reza / Hentati, Faycal / Hockley, Maryam M / Hölbling, Benedikt / Schwarzmayr, Thomas / Karimiani, Ehsan Ghayoor / Kernstock, Christoph / Maroofian, Reza / Müller-Felber, Wolfgang / Ozkan, Ege / Padilla-Lopez, Sergio / Reich, Selina /

Reichbauer, Jennifer / Darvish, Hossein / Shahmohammadibeni, Neda / Tafakhori, Abbas / Vill, Katharina / Zuchner, Stephan / Kruer, Michael C / Winkelmann, Juliane / Jamshidi, Yalda / Schüle, Rebecca

Nature communications

2019 Volume 10, Issue 1, Page(s) 4790

Abstract: Alterations of ... ...

Abstract	Alterations of Ca
MeSH term(s)	Adolescent ; Adult ; Animals ; Calcium/metabolism ; Cell Line, Tumor ; Child ; Child, Preschool ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum-Associated Degradation/genetics ; Female ; Fibroblasts/metabolism ; Gene Knockdown Techniques ; High-Throughput Nucleotide Sequencing ; Humans ; Inositol 1,4,5-Trisphosphate/metabolism ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; Male ; Middle Aged ; Neurons/metabolism ; Primary Cell Culture ; Signal Transduction ; Skin/cytology ; Spastic Paraplegia, Hereditary/genetics ; Spastic Paraplegia, Hereditary/metabolism ; Ubiquitin-Protein Ligases/genetics ; Zebrafish
Chemical Substances	Inositol 1,4,5-Trisphosphate Receptors ; Inositol 1,4,5-Trisphosphate (85166-31-0) ; RNF170 protein, human (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2019-10-21
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-019-12620-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

Search results

Search options

Article ; Online: An iPSC model for POLR3A-associated spastic ataxia: Generation of three unrelated patient cell lines.

More links

Kategorien

Order via subito

Article: Unraveling Axonal Transcriptional Landscapes: Insights from iPSC-Derived Cortical Neurons and Implications for Motor Neuron Degeneration.

More links

Kategorien

Inter-library loan at ZB MED

Article ; Online: The kinesin motor KIF1C is a putative transporter of the exon junction complex in neuronal cells.

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Article ; Online: Generation of the CRISPR/Cas9-mediated KIF1C knock-out human iPSC line HIHRSi003-A-1.

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Article ; Online: Generation of two iPSC lines derived from two unrelated patients with Gaucher disease.

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Article ; Online: Calpastatin ablation aggravates the molecular phenotype in cell and animal models of Huntington disease.

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Article ; Online: A combinatorial approach to identify calpain cleavage sites in the Machado-Joseph disease protein ataxin-3.

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Article ; Online: Bi-allelic variants in RNF170 are associated with hereditary spastic paraplegia.

More links

Kategorien

Order via subito