Epigenetic mechanisms underlying dendritic atrophy in ALS

Motor neurons are made up of three distinct regions. The top of the neuron is composed of branches like a tree called dendrites that receive information to transmit. The middle part of the neuron is called the cell body where the majority of the life processes occur and the bottom consists of a single long wire, called an axon that connects the neuron to the next neuron in the chain or to the muscle for movement. Electrical signals in the brain are received in the dendrites of upper motor neurons, transmitted along the neuron to the connection between its axon and the dendrites of the lower motor neuron, and then transmitted along the lower motor neuron to the muscle, causing it to contract. In ALS, these connections are broken when motor neurons degenerate and the brain can no longer signal the muscles, leading to paralysis. Most research has focused on the cell body and the axon, but the dendrites also play an important role in ALS and they have been demonstrated to shrink during disease. In this study, Dr. Durham’s lab will examine why dendrites shrink in ALS and attempt to identify ways to prevent it. Dr. Durham’s lab specializes in recreating ALS-like conditions in motor neurons living in a dish (cell culture) by giving them abnormal genes that cause the disease in humans. Preliminary findings in these motor neurons suggest a specific genetic pathway that might be affecting dendrite health. Determining if this pathway is important will not only provide an important addition to our understanding of ALS, but also a potential target for treating the disease.