Dr Andrew Tosolini, an MNDRA grant recipient from the University of Queensland, has provided us with an excellent summary of the work he has been undertaking. Dr Tosolini and his team have received funding from multiple sources, including MND Australia, and this funding has supported this vital work.
Motor neurons are nerve cells that enable voluntary muscle movements like walking, talking, and breathing. They send electrical signals from the brain and spinal cord to muscles along thin, cable-like structures called axons. In MND, motor neurons gradually stop working and die, leading to muscle weakness and paralysis. Each motor neuron axon is wrapped in an insulating layer of a fatty substance called myelin – very much like how electrical wires can be insulated with rubber. However, unlike wires, there are frequent and organised gaps in the myelin known as nodes of Ranvier. These uninsulated regions act like relay stations to boost electrical signals as they travel down the motor neuron toward the muscle.
Most people only think about the electrical signals that travel from the spinal cord to muscles to generate movements. However, there are also many different substances that move back and forth along the axons. This process is called ‘axonal transport’, which acts like a delivery system within nerve cells. As the distance connecting the spinal cord to muscle can be quite large (e.g., up to 1 metre long), an effective transport system is critical for delivering substances along the length of the nerve and keeping motor neurons healthy. Essential supplies, like energy (from mitochondria) and survival signals (from signalling endosomes), are constantly shuttling back and forth between the spinal cord and muscle. Tiny “trucks” (motor proteins) carry these supplies along the “highways” (axons) to ensure the neuron functions properly.
Our previous research has shown that degeneration of motor neurons disrupts the transport of essential cellular components, which contributes to the progression of MND. Using advanced imaging techniques, our recently published study found that at the nodes of Ranvier, both the mitochondria (generates energy) and signaling endosomes (carrying messages from the muscle) slow down and pause more as they pass through the uninsulated regions of the axon. These cargoes then speed up again once they exit these regions. This research has defined how the system works in healthy conditions, but because the nodes of Ranvier are also affected in MND, understanding if this transport system is also compromised is a future priority. By understanding exactly what goes wrong in MND, we can design effective therapies to correct and restore function of the motor neurons.
To read the paper in full, please visit Science Direct
