Researchers will use “fluorescence imaging biosensors” to visualize biochemical signals within neurons derived from embryonic stem cells to test whether these neurons respond appropriately to molecular guidance cues. The guidance cues to be tested regulate the orientation the axons (communication cables) of developing and regenerating neurons, which controls neural network formation, necessary for stem cell therapy to benefit patients with Parkinson’s disease.
Parkinson’s disease progressively depletes neurons that use the transmitter dopamine to communicate with one anther. While the drug L-DOPA is effective in controlling symptoms for a long period in most patients, eventually the drug’s effectiveness is severely compromised. Researchers have been experimenting with stem cell therapy to determine whether the stem cell-derived neurons can effectively be reincorporated into the correct neural networks. To do so, stem cell-derived neurons need to respond to environmental factors that attract of repel outgrowth, to guide axon extension in the correct direction. Improperly activated signals can cause mis-wiring of the axons.
The researchers hypothesize that modulation of specific signaling pathways must occur with precise spatial and temporal control, as occurs in developing neurons. They will use fluorescence imaging to determine whether two key biochemical signals are activated normally within dopaminergic neurons derived from stem cells. If improper activation of one or both signals occurs, this information will help to identify the proteins that are necessary to effectively guide the axons of stem cell-derived neurons to their appropriate targets in Parkinson’s disease.
Significance: This research provides a new direction for correcting defects in cultured stem cells that might be used to treat Parkinson’s disease.