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Aberrant gene | Differentiated cell type | Main observations | Associated disease | Reference |
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C9ORF72 | hiPSC derived neurons | RNA foci, RAN translation products, and increased susceptibility to cellular stress caused by autophagy inhibition | ALS/FTD | [22] |
hiPSC derived neurons | Specific susceptibility to glutamate excitotoxicity and mitigation of C9ORF72 phenotype with antisense oligonucleotides therapeutics | ALS/FTD | [23] |
hiPSC derived MNs | Transcriptional changes and presence of RNA foci | ALS/FTD | [24] |
|
C9ORF72/TARDBP | hiPSC derived MNs | Neuronal hyperexcitability followed by progressive loss of action potential output and synaptic activity | ALS/FTD | [52] |
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PGRN | hiPSC derived neurons | Increased sensitivity to kinase inhibition, reduced S6K2 levels, and neurite degeneration in absence of glia | FTD | [19] |
hiPSC derived neurons | Identification and validation of small molecules with therapeutic potential | FTD | [53] |
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TARDBP | hiPSC derived MNs | Mislocalization of TDP-43, decreased MN survival rate, and increased vulnerability to inhibition of the PI3K pathway | ALS/FTD | [17] |
hiPSC derived MNs | Identification of the histone acetyltransferase inhibitor anacardic acid as able to reverse disease phenotype | ALS/FTD | [35] |
hiPSC derived MNs | TDP-43 aggregation and feasibility of hiPSCs derived MNs for drug screening | ALS/FTD | [21] |
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TARDBP/SOD1 | mESC derived MNs/hiPSCs derived MNs | Kenpaullone, a GSK3-inhibitor, increased survival of MNs more so than two potential therapeutic compounds that failed in clinical trials (olesoxime and dexpramipexole) | ALS | [32] |
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SOD1 | hESC derived MNs/glia cells | MNs were shown to be selectively sensitive to toxic effects of cocultured SOD1 glial cells | ALS | [30] |
hESC derived MNs/astrocytes | Selective MN toxicity correlates with increased inflammatory response in SOD1 astrocytes | ALS | [31] |
hiPSC derived MNs | Identification of misregulated neurofilament | ALS | [27] |
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SOD1/C9ORF72 | hiPSC derived MNs | Potential correlation between SOD1 and C9ORF72 pathogenesis, including elevated oxidative stress response | ALS | [20] |
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