When nerve cells in the brain die, diseases such as Alzheimer's and Parkinson's develop. To protect these cells, there are immune cells in the brain known as microglia. A study has now shown that microglia form tiny tubes, so-called ‘tunneling nanotubes’, and thus connect directly to the nerve cells. The microglia can transport harmful proteins away and supply vital substances via the tubes. These findings are important for the treatment of neurodegenerative diseases.

In diseases such as Parkinson's and Alzheimer's, harmful protein clumps form in the neurons. It was previously assumed that microglia only take up these clumps after dead nerve cells release them. ‘We have known for a long time that microglia clean up these toxic proteins as soon as they are released,’ says Hannah Scheiblich, research group leader at the Max Planck Institute for Biology of Ageing and lead author of the study.

Exchange via tubes
The new study shows that microglia can use the tubes to remove these harmful proteins directly from the neurons before they cause severe damage. In addition, the microglia send healthy mitochondria, the so-called power plants of the cells, to stressed neurons through these tubes, reducing stress and allowing the neurons to function better despite illness. Co-author Frederik Eikens added: ‘We are excited by these results and the potential to directly intervene in neuronal health by improving the natural functions of microglia.’

The study also found that certain genetic mutations in microglia affect the formation and function of the tubules. These mutations are associated with a higher risk of neurodegenerative diseases, suggesting that problems in tube formation may contribute to these diseases. ‘Our next steps will focus on understanding how these tubules are formed and finding ways to boost this process in disease,’ says co-author Lena Wischhof.

‘These findings change our understanding of how microglia support brain health,’ say Hannah Scheiblich and Michael T. Heneka from the Luxembourg Centre for Systems Biomedicine. By demonstrating that microglia actively maintain neuronal health with the help of the tubes, they have identified new potential avenues for treating neurodegenerative diseases. The research team will now focus on learning more about the formation of these tubes between cells and developing therapies that improve the support of neurons by microglia.