NeuroQuality

Eurac Research acts as collaborator in aim 3 of NeuroQuality project: The role of ribosome quality control (RQC) in neurodegeneration - In vivo study of RQC

Perhaps the most intriguing question regarding RQC in humans is why specific mutations of RQC factors lead to neuronal and neurodegenerative disorders. Here, several plausible hypotheses can be generated, based on the extreme morphology of neuronal cells, their distinct proteome or their susceptibility to stress. For instance, it was shown that spatial limitation within dendritic spines and axonal boutons results in translation driven by the monosomes (as opposed to polysomes), which results in specific local proteome. We propose that such neuronal characteristics can represent a challenge for the RQC and protein degradation pathways leading to increased protein aggregation. To test this hypothesis we will utilize the C. elegans model system whose RQC components are highly evolutionary conserved and its biological complexity should reveal novel aspects of RQC biology. Specifically, we will determine the temporal and spatial distribution of RQC components in neurons compared to other tissues (aim 3.2.1) and the effect of RQC/degradation deficiency on cellular proteostasis and neurodegeneration (aim 3.2.2). These in vivo studies should elucidate the role of eIF5A in RQC and test our hypothesis of limited RQC activity in neuropils as a cause of neurodegeneration. In addition, our future plans also aim to use the newly generated C. elegans model of RQC activity in genetic screens seeking new regulators of RQC activity (see Future Directions).