DiscussionDisease modalities such as Parkinsonï¿½s, ALS and Alzheimerï¿½s represent complex neurological disorders where certain neuronal populations decline via only partially understood mechanisms that frequently involve neuro-inflammation.
- Identify new and disease-relevant, neuroprotective compounds for ALS.
- Model the non-cell autonomous nature of ALS by integrating stem cell-derived motor neurons, astrocytes and activated microglia
- Screenable phenotypic assay that uses degeneration of motor neurons as primary readout
Diverse secondary assays for mechanism of action studies
- Identified a small number of neuroprotective compounds in a screen of 11,000 compounds.
- Hit compounds shown to act through multiple
- inhibition of microglial activation,
- directed protection of neurons from NO stress
- glia-specific activation of genes controlled by Nrf2 transcription factor