In vitro assessment of Tau aggregation
With a lentiviral transduction of Tau and chronic treatment with Tau PFFs of Ncardia’s human iPSC-derived cortical neurons we can recapitulate the increase in MC-1 and phospho-Tau, the initial stages of protein aggregation. Formation of insoluble Tau aggregates is also modeled as demonstrated by the results after treatment with methanol.
In vitro assessment of Tau aggregation in human iPSC-derived neurons using High Content Imaging
In vitro assessment of α-Synuclein aggregation
Acute treatment of Ncardia’s human iPSC-derived cortical neurons with PFFs induces a significant increase in the formation of puncta phospho- α-Syn when compared to untreated neurons. Chronic treatment can further increase the phenotype. To show the potential of the assay, disease neurons were treated with inhibitors of the protein degradation pathway and activators of lysosomal activity. Both treatments showed the expected phenotype rescue effect.
In vitro assessment of a-synuclein aggregation in human iPSC-derived neurons using high content imaging
In vitro assessment of TDP-43 aggregation
We have developed a protocol for the maturation of human iPSC-derived motor neurons with both wild type and TDP-43 CRISPR engineered lines*. After maturation, mutant TDP-43 motor neurons show mis-localization and aggregation of TDP-43. Addition of a chemical stressor can further enhance the phenotype. Based on this model, we have optimized a HTRF assay to quantify the aggregation of TDP-43 as part of the Proteinopathy Exploration Package. Additional assays for TDP-43 mis-localization and STMM2 mis-splicing are also available at Ncardia.
* iCell(R) Motor Neurons, 01279 from FUJIFILM Cellular Dynamics, Inc
Quantification of the normalized TDP-43 aggregation in human iPSC-derived motor neurons by HTRF
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