The role of astrocytes in early pathogenesis of motor neuron disease: a mechanistic study of neuronal degeneration and synaptic alterations

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Motor neuron disease (MND) is a rapidly disabling condition, leading to generalized muscle weakness and finally to death most commonly by paralysis of breathing muscles. The patients' quality of life is significantly reduced during the median survival time of three years not only by physical disabilities but also by dementia to a variable degree. In the UK 1 in 300-500 people are at risk of developing this disease, affecting about 5000 people at any time. It is untreatable and there is urgent need to develop successful therapies. In order to achieve this we need to understand the problems occurring in nerve cells, called neurons and also in their surroundings.The immediate issue causing disability is within motor neurons, specialized nerve cells that normally convey electrical impulses to achieve muscle contraction. However, a major breakthrough in MND research identified that glial cells involved in supporting the function of neurons can be diseased too. Astrocytes, a type of glial cell that closely interact with motor neurons, have been shown to directly harm or to disrupt important cross-talk between them, resulting in muscle weakness. These mechanisms commonly occur in MND, providing a logical target for new treatments.Over the last decade as a researcher and practicing neurologist, my work was based on understanding the dialogue between astrocytes and neurons. Establishing a research group at the University of Cambridge, we have made fundamental observations supporting the idea that by default astrocytes are meant to repair damaged motor neurons. Now, I also assembled innovative collaborations to develop my skill-set and to use state-of-art models relevant to human disease to identify what goes wrong in the astrocyte and motor neuron relationship. The ultimate aim of this work is to gain insight that can help us to treat (and even possibly cure) MND.