| Outline of Final Research Achievements |
The accumulation of misfolded proteins formed upon disruption of intracellular proteinstasis often results in the formation of aggregates in the cell. Such protein aggregates are thought to be toxic and cause death of neurons. However, the mechanism of reducing the toxicity of the aggregates formed in the cells at the individual level has not been elucidated, and its application to the treatment of specific neurodegenerative diseases has not been possible. In this study, we established a nematode strain expressing TDP25, a causative protein of amyotrophic lateral sclerosis (ALS), and analyzed its motility and lifespan. We further established a novel fluorescence spectroscopy method and a system to read out the structure of RNAs that bind to aggregate proteins in living cells. We also established a method to read out the status of intracellular macromolecular crowding, which is thought to be involved in aggregation formation, using the fluorescence lifetime of GFP.
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