Assessing the therapeutic impact of chemogenetic stimulation of neuropeptide Y cortical interneurons in MND mouse models

Motor neurone disease (MND) is a fatal neurodegenerative disease with no effective treatment. Nerve cells (also known as motor neurons) in the motor regions of the brain carry signals to the spinal cord which, in turn, communicate with muscle to control movement.

In people with motor neurone disease, brain and spinal cord motor neurons deteriorate and can no longer carry these signals, resulting in progressive muscle weakness, paralysis and death typically by respiratory failure.

The loss of both brain and spinal cord motor neurons is postulated to result from chronic neuronal overactivity – increasingly recognised as an important pathological factor in motor neurone disease. Importantly, the activity of brain motor neurons is modulated by inhibitory neurons or interneurons, whereby reduced interneuron activity is associated with motor neuron overactivity. Indeed, cortical interneurons are lost in MND patients and mouse models. One way to attenuate overactive brain motor neurons is to increase the activity of cortical interneurons.