Clock expressing neurons (magenta) showed no ER stress (green) in the neurodegenerative fly brain.

A major hallmark of neurodegeneration (e.g., FTD, AD, PD and HD) is misfolded protein aggregates in affected brains. Protein misfolding leads to ER stress and triggers a signal network called Unfolded Protein Response (UPR). Prolonged ER stress eventually causes neuronal dysfunction. However, it is unclear what underlying molecular mechanisms determine such neurodegenerative processes to target selective brain areas. Intriguingly, data indicates that the presence of the circadian clock may facilitate or inhibit the formation of pathogenic aggregates depending on the types of misfolded protein aggregates. We plan to use molecular tools including ER stress reporter, Flowcytometry and clock neuron transcriptome to identify the underlying neuroprotective molecular mechanisms.