Global survey of endogenous substrates for Hero proteins upon proteostasis dysfunction and implication in anti-aggregation strategy.

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Different chemical insults to mimic proteostatic disbalance such as Proteasome inhibition, autophagy inhibition and chaperone inhibition were used to induce the protein aggregation. Hero proteins were surveyed globally for their natural clients to potentially minimize the aggregation formation by their co-expression. Filter trap method was mostly used to investigate global aggregation and aggregating proteome wide study was extended by mass spectrometry. Top hit aggregating protein candidates which could be possibly co-localized with the Hero proteins were validated such as Hero9 might have essential function in stabilizing the candidate proteins in nucleolus to maintain the ribosome biogenesis. It is still the subject of study what properties of these aggregating proteins could be important for the action of Hero proteins for their disaggregation properties.Yet number of other aggregating clients for each of the Hero proteins (Hero7, Hero9, Hero11, Hero13, Hero20, Hero45) were studied upon proteasome inhibition system-wide utilizing mass spectrometry after the filter trapping process. This technique is novel approach to study the aggregating proteins in system-wide manner which is essentially modified from the classical technique of filter trapping the aggregates. Further, the future study will imply for the mechanism of endogenous protein stabilization to relieve their potential aggregation and functionality of that proteins preventing the physiological disorders such as neurological disorders.