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Cytometry based screening on cell - based models of neurodegeneration


, : Cytometry based screening on cell - based models of neurodegeneration. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 335 2

TROPHOS screens for neurotrophic compounds using live primary neurons and a novel instrument, the FLASH CYTOMETER(R), that images entire wells of standard microplates and counts live neurons accurately, reproducibly and rapidly. This instrument enables development of mechanism-based assays using the specific neurons affected in a neurodegenerative disorder. The approach has been validated using a trophic factor deprivation model to screen a 40,000 compound library for small molecules that promote motor neuron survival. Lead molecules are now being characterized for mechanism of actin and optimized for activity, bioavailabiliy and safety. Additional models of motor neuron cell death are advancing into the screening phase. For Huntington's Disease, we have developed a cell-based assay that mimics the disease process using primary striatal neurons. When these neurons are transfected with a fragment of huntingtin containing 68 CAG repeats (Htt-68Q), 50% of the transfected cells die after a week in culture. These cells can be rescued by BDNF. We are currently using this system to screen for molecules that prevent Htt-68Q mediated cell death. We demonstrate how the FLASH CYTOMETER(R) is used to perform high throughput screening using these models.

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