Measuring Proteostasis Imbalance in Health and Disease
Proteostasis describes the maintenance of the proteome in a folded state by an extensive quality control network. Proteostasis governs protein synthesis, folding, degradation and suppresses proteins from aggregating. When proteostasis fails or becomes overwhelmed the proteome becomes unstable and protein aggregation is observed. A suite of neurodegenerative diseases display markers of dysfunctional proteostasis, including protein aggregation as the most central feature of pathology. For example, Huntingtin protein aggregation is a hallmark of Huntington's disease and TDP-43 aggregation (as well as other proteins) are a core feature of most forms of Motor Neuron Disease. The importance of proteostasis is illustrated by treatments that modify proteostasis as being on the list of highest priorities for HD clinical trials.
Our team has invented new methods to measure how imbalanced proteostasis is using biosensor technologies. We are using these methods to understand fundamentally how the quality control systems adapt to stresses in cell culture and simple animal model systems (nematode).
We are also working with clinicians at the Royal Melbourne Hospital to investigate the applicability of the technology in detecting presymptomatic measures of proteostasis imbalance which holds great promise as a clinically relevant diagnostic tool.
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