Neurons Induced From Fibroblasts of c9ALS/FTD Patients Reproduce the Pathology Seen in the Central Nervous System
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023884%3A_____%2F19%3A00008233" target="_blank" >RIV/00023884:_____/19:00008233 - isvavai.cz</a>
Result on the web
<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743368/" target="_blank" >https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743368/</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3389/fnins.2019.00935" target="_blank" >10.3389/fnins.2019.00935</a>
Alternative languages
Result language
angličtina
Original language name
Neurons Induced From Fibroblasts of c9ALS/FTD Patients Reproduce the Pathology Seen in the Central Nervous System
Original language description
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are incurable neurodegenerative conditions. A non-coding hexanucleotide (GGGGCC) repeat expansion in the c9orf72 gene is the most common genetic cause of ALS/FTD. We present a cellular model of c9ALS/FTD where induced neurons (iNeurons) are generated within 2 weeks by direct conversion of patients' dermal fibroblasts through down-regulation of polypyrimidine-tract-binding protein 1 (PTB1). While sense (S) and antisense (AS) intranuclear RNA foci were observed in both fibroblasts and iNeurons, the accumulation of (S) and (AS) repeat-associated non-ATG translation (RANT) products were detected only in iNeurons. Importantly, anti-sense oligonucleotides (ASOs) against the (5) repeat transcript lead to decreased (5) RNA foci staining and a reduction of the corresponding RANT products without affecting its (AS) counterparts. ASOs treatment also rescued the cell viability upon stressful stimulus. The results indicate that iNeurons is an advantageous model that not only recapitulates c9ALS/FTD hallmark features but can also help uncover promising therapeutics.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
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Continuities
N - Vyzkumna aktivita podporovana z neverejnych zdroju
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Frontiers in Neuroscience
ISSN
1662-453X
e-ISSN
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Volume of the periodical
13
Issue of the periodical within the volume
September
Country of publishing house
CH - SWITZERLAND
Number of pages
10
Pages from-to
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UT code for WoS article
000484547600001
EID of the result in the Scopus database
2-s2.0-85072840163