Body's 'bomb squad' can help fight brain tumours: Study

Scientists have discovered how a molecule can help prevent certain types of brain tumours by recognising and 'disarming' harmful proteins that cause them.

The study in fruit flies, published in the journal eLife, could lead to a potential new treatment approach for brain tumours in future.

Most multicellular organisms possess a one-way cell signalling pathway called Notch signalling, which is crucial for embryonic development.

The correct establishment and maintenance of Notch signalling are critical for ensuring a balance in the number of stem cells that occur in the body and brain.

"Abnormal activation of Notch signalling in neural progenitors -- which send signals to neural stem cells -- can cause an excess of these stem cells to occur in the brain, and this can in turn lead to brain tumour development," said Bo Li from Peking University in China.

"However, the molecular mechanisms that prevent abnormal Notch signalling activation and potentially harmful decisions related to cell fate remain unclear," Li said.

The researchers carried out genetic and biochemical tests to study stem cells called neuroblasts in the central brain region of fruit fly larvae.

They looked in particular at the retromer protein complex, which transports specific cargo proteins from endosomes, a type of membrane-bound compartment inside cells, to the cell surface.

Their analysis revealed that the retromer complex regulates Notch protein trafficking in neural progenitors.

When the complex is inactive, Notch receptors are activated incorrectly, transforming the progenitors into an excess number of neural stem cells and increasing the risk of brain tumour formation.

"We found that a sufficient amount of Notch protein needs to be destroyed in neural progenitors to maintain the one-way Notch signalling pathway between these progenitors and neural stem cells," said Chouin Wong, a graduate student at Peking University.

"When an excess of Notch protein fails to be destroyed in neural progenitors, this is normally recognised by the retromer complex and is rapidly transported away from the endosomes inside cells.

"But when the retromer complex is inactive, this pool of Notch protein increases massively in the endosomes and is 'ignited' abnormally," said Wong.

These results led the team to propose a model whereby the retromer complex serves as a kind of 'bomb squad' to retrieve and disarm the potentially harmful pool of incorrectly activated Notch receptors in a timely manner, thereby preventing the risk of brain tumours forming in this way.