Extracellular Proteostasis

Impact: A new field of research opening up avenues for understanding and treating age-related diseases

Understanding the biological process of ageing, and age-related diseases, is critical to the development of therapies which may treat – or even cure – conditions such as Alzheimer’s disease.

Professor Mark Wilson's research group, with help from colleagues at the UOW Proteostasis and Disease Research Centre, are opening up a new field of research – extracellular proteostasis – that is providing crucial new information about our knowledge of ageing and disease.

Extracellular proteostasis is the study of the biological processes that sense and regulate damaged proteins in body fluids like blood plasma and the cerebrospinal fluid.

Proteins are important biological molecules that must keep a normal (native) shape in order to function correctly, but everyday ‘wear and tear’ can cause them to lose their shape over time. When this happens they become ‘sticky’ and can form toxic aggregates, or lumps, that can kill brain cells and damage the body in a variety of ways.

A loss of the ability to control these sticky proteins has been strongly implicated in underlying a variety of serious human diseases, including Alzheimer's disease and Type II diabetes, and the ageing process itself.

Although around 30 years of research has identified many mechanisms that operate inside cells to defend against damaged proteins, the corresponding processes that operate in the five litres of human body fluids were previously largely unknown.

The quality of extracellular proteostasis research at UOW received global recognition via an invited review by Professor Wilson in the prestigious Annual Review of Biochemistry journal in 2013.

Previous work by Professor Wilson's group led to the world-first discovery of special molecules, called extracellular chaperones, in body fluids that act to shield us from the toxicity of damaged proteins and help clear them from the body. This finding is the basis of a UOW project to ‘drug’ a chaperone in blood to combat diseases.

In future, Professor Wilson's research group will continue to investigate and understand the mechanisms that recognise and clear damaged and dangerous protein molecules from body fluids, facilitating the development of new strategies to combat the effects of ageing and serious diseases.