[
International Worm Meeting,
2015]
Protein aggregation is caused by a multitude of factors; there could be specific environmental causes like oxidative stress, or a genetic predisposition to aggregation. Protein aggregation increases with aging, as the ability to rectify or clear misfolded proteins is reduced. This is partly due to age-dependent deterioration in the ubiquitin/proteasomal system or other unfolded protein response systems. Aggregation will be enhanced when a misfolded, dysfunctional protein does not undergo degradation via normal pathways like autophagy/lysosome or ubiquitin proteasome-mediated degradation pathways. By mass spectrometry, we identified several proteins in the aggregates of a C. elegans model of Huntington's Disease. The effects on protein aggregation, of RNAi-mediated knockdown of some of these proteins, were tested. Some of the gene knock downs by RNAi altered the extent of aggregation in C. elegans, suggesting that these could act as seed proteins and enhance the progression of aggregates. These can be useful targets to disrupt the aggregates and could be exploited for therapeutic interventions in neurological diseases.