On World Brain Day (22 July), we’re taking a look at the work of two Crick neuroscience labs, aiming to understand the very early stages of neurodegenerative diseases, and inform how we treat or prevent these conditions. Both labs look at astrocytes, star-shaped support cells in the brain that may play a bigger role in disease development than originally thought.

Stopping astrocyte stress in motor neurone disease

Motor neurone disease (MND) is an incurable neurodegenerative condition affecting the brain and spinal cord, where the degeneration of motor neurons causes progressive muscle weakness.

Scientists in the Human Stem Cells and Neurodegeneration Laboratory, led by Rickie Patani, use skin cells from patients with genetic forms of MND and reprogram them into stem cells, which can then be ‘transformed’ into neurons and astrocytes.

"It’s like restarting the clock on the cells", says postdoctoral researcher Hannah Franklin. "This lets us find very early disease mechanisms, which is important as most people are diagnosed only once the damage in their brain is already quite advanced."

Cell stress is a key problem in neurodegenerative diseases, including MND. If a cell becomes stressed due to an external or internal trigger, it can require more oxygen to cope with the stress and can enter a state where this stress response is continually activated, which in turn can be dangerous.

Hannah’s research involves interrogating this further by studying astrocytes. Her work shows that it’s not just neurons that can become dysfunctional in MND – astrocytes too show clear signs of stress. This could cause them to lose their protective functions and progressively damage nearby neurons. 

Hannah believes the future of MND treatment and prevention has to be personalised, as the disease manifests differently from person to person.

We haven’t yet found a way to treat MND by focusing just on neurons. You can’t look at cells in isolation, because there’s crosstalk between all different types of cells in the brain and spinal cord, including between astrocytes and neurons. If we know why and how astrocytes are becoming diseased, and how to switch them back to a healthy state, we might be able to prevent the degeneration of neurons.”

We need a toolkit to understand what mechanisms are disrupted in different people and how to identify them earlier,” said Hannah. “For patients, understanding what’s happening to them can bring them peace, but one day better treatments and diagnosis might be able to offer even more concrete hope.

– Hannah Franklin, postdoctoral researcher, Patani lab

Clearing out faulty mitochondria via astrocytes in Parkinson’s disease

The Mitochondrial Neurobiology Laboratory, led by Mike Devine, looks at how synapses – junctions where messages are carried from cell to cell – can be impacted in Parkinson’s disease, a neurodegenerative condition involving cell death in regions of the brain related to motor function.

Although the brain is just 2% of body mass, it uses 20% of the body’s energy, and a lot of this is needed for communication via synapses. The team focus on parts of the cell called mitochondria, the batteries powering brain activity.

There’s evidence that the brain aims to protect against disease by transferring dysfunctional mitochondria out of neurons and into astrocytes, and healthy mitochondria from astrocytes into neurons. We don’t really understand how these mitochondria are transferred yet, but this mitochondrial transfer could help to maintain a functioning energy source for neurons which is important for brain health.

– Katy Hole, postdoctoral project research scientist, Devine lab

If the team can work out how to support the exchange of dysfunctional mitochondria, this could help to improve the health of neurons in the early stages of Parkinson’s disease and stop it from progressing. Although it’s a while before this could be a viable treatment, the team plan to screen for compounds that could boost this transfer.

Yulia Sudarikova is also looking at mitochondrial dysfunction, but she’s specifically aiming to understand what impact this has on presynaptic cells, which release messages into the synapse.

In the lab, she is working on selectively damaging mitochondria in axons (the fibres carrying messages in the neuron) and seeing if they are degraded or repaired locally.

We’re now understanding that synapses break down before the cells die, so this could represent an early stage of the disease. Because we can’t regenerate brain cells, it’s crucial to understand these early disease processes and how we can target them.

– Yulia Sudarikova, PhD student, Devine lab

Hello Brain! exhibition

Remember that our free public exhibition, Hello Brain!, is open in the Manby Gallery until December 2024. It highlights Crick research aiming to advance our understanding of the brain, from the early beginnings of neuroscience to recent discoveries and technological progress.