New South Australian research will seek to uncover how the brain’s defence systems identify and remove damaged proteins, paving the way for new approaches to preventing and treating dementia.
Dr Julian Carosi, a researcher in the Lysosomal Health in Ageing group at SAHMRI and Adelaide University, has been awarded a major National Health and Medical Research Council (NHMRC) Investigator Grant to lead a five-year research program to understand exactly how cells are able to detect and dispose of faulty proteins before they can accumulate and cause harm.
“Damaged proteins such as Tau can become sticky, form aggregates and accumulate in the brain, where they contribute to the death of neurons and the progression of neurodegenerative disease,” Dr Carosi said.
“Cells have sophisticated systems for detecting and clearing these proteins, but we still know remarkably little about how they distinguish damaged proteins from healthy ones.”
Proteins carry out essential functions throughout the body, but when they become damaged they can clump together and build up inside cells. This toxic accumulation is a hallmark of Alzheimer’s disease and other forms of dementia.
The project will investigate how cells recognise damaged proteins, why some toxic protein aggregates escape the body’s natural defence systems, and whether those pathways could be harnessed to develop new therapies.
At the heart of Dr Carosi’s research is autophagy, the body’s process of breaking down and recycling damaged cell components to keep them functioning properly.
Scientists know autophagy is critical to maintaining healthy brain function, but the mechanisms that allow cells to recognise damaged proteins remain a mystery.
“My goal is to uncover how these damage-sensing systems work at a molecular level and explore ways to redirect them to selectively destroy harmful proteins before they can drive disease.”
It’s hoped the project will provide valuable new insights into one of the fundamental biological processes underpinning neurodegenerative diseases that affect millions of people worldwide.
“If we can learn how cells naturally identify and remove damaged proteins, we may be able to develop entirely new approaches to treating or even preventing these diseases.”