Researchers have discovered how to block cells from dying, in a finding that could lead to new treatments for neurodegenerative conditions like Parkinson's and Alzheimer's. The team at WEHI, including researchers from the Parkinson's Disease Research Centre, have identified a small molecule that can selectively block cell death.

Published in Science Advances, the findings, titled "Differential regulation of BAX and BAK apoptotic activity revealed by small molecules," lay the groundwork for next-generation neuroprotective drugs for degenerative conditions, which currently have no cure or treatments to stop their progression.

A new hope in the fight against degenerative conditions

Millions of cells are programmed to die in our bodies every day. But excessive cell death can cause degenerative conditions I, including Parkinson's disease and Alzheimer's disease, with the premature death of brain cells a cause of symptoms in these diseases.

Professor Grant Dewson, co-corresponding author and head of the WEHI Parkinson's Disease Research Centre, said, "Currently, there are no treatments that prevent neurons from dying to slow the progression of Parkinson's. Any drugs that could be able to do this could be game-changing."

The new study aimed to find new chemicals that block cell death and could be useful to treat degenerative diseases in the future.

To identify novel small molecules, the team worked with researchers in the National Drug Discovery Centre, headquartered at WEHI. A high-throughput screen of over 100,000 chemical compounds identified one that was effective at stopping cells from dying by interfering with a well-understood cell death protein.

Co-corresponding author Professor Guillaume Lessene said, "We were thrilled to find a small molecule that targets a killer protein called BAX and stops it working. While not the case in most cells, in neurons, turning off BAX alone may be sufficient to limit cell death."

Building on decades of pioneering cell death research

The new research builds on decades of WEHI discoveries in cell death. A pioneering discovery at WEHI in 1988 of a protein that stopped programmed cell death sparked huge interest in the field and has since led to a new drug to treat cancer.

While drugs that trigger cell death are transforming the treatment of certain cancers, the development of cell death blockers, which could be similarly game-changing for neurodegenerative conditions, has proven challenging.

The new molecule targets a killer protein called BA, X, which kills cells by damaging mitochondria.

Lead author and Dewson Lab researcher Kaiming Li said, "For the first time, we could keep BAX away from mitochondria and keep cells alive using this molecule. This could pave the way for next-generation cell death inhibitors to combat degenerative conditions."

The study demonstrates the potential to identify drugs that block cell death and may open a new avenue to find much-needed disease-modifying drugs for neurodegenerative conditions such as Parkinson's and Alzheimer's.

The WEHI Parkinson's Disease Research Centre is focusing on its expertise in cell death, ubiquitin signalling, mitochondria and inflammation in the hunt for disease-modifying therapies for Parkinson's. By using a multidisciplinary approach to build understanding of the mechanisms behind the disease, the centre hopes to accelerate the discovery of drugs to stop disease progression, transforming the lives of those living with the condition.