Investigating Coordinated Removal of Old and Synthesis of New Materials in Neurons and how These Processes are Disrupted in FTD

Similar to how grocery stores maintain a full shelf of milk cartons by continually selling milk and obtaining new cartons, cells must balance the removal of old and synthesis of new materials. In neurons, insufficient removal of materials or defects in synthesis, lead to loss of neuronal function, accumulation of toxic aggregates, and ultimately neuron death, contributing to the pathogenesis of neurodegenerative diseases such as Frontotemporal Dementia (FTD). In this proposal I will examine how the distinct processes of removal and synthesis are interrelated. I will use imaging to determine their physical and temporal relationship, drugs to block removal and determine the effects on synthesis, and I will use neurons created from human cells to best determine the extent to which these processes occur during FTD.

Similar to how grocery stores maintain a full shelf of milk cartons by continually selling milk and obtaining new cartons, cells must balance the removal of old and synthesis of new materials. In neurons, insufficient removal of materials or defects in synthesis, lead to loss of neuronal function, accumulation of toxic aggregates, and ultimately neuron death, contributing to the pathogenesis of neurodegenerative diseases such as Frontotemporal Dementia (FTD). In this proposal I will examine how the distinct processes of removal and synthesis are interrelated. I will use imaging to determine their physical and temporal relationship, drugs to block removal and determine the effects on synthesis, and I will use neurons created from human cells to best determine the extent to which these processes occur during FTD.