Importance of lipids for upper motor neuron health and disease

Building evidence reveals the importance of maintaining lipid homeostasis for the health and function of neurons, and upper motor neurons (UMNs) are no exception. UMNs are critically important for the initiation and modulation of voluntary movement as they are responsible for conveying cerebral cortex' input to spinal cord targets. To maintain their unique cytoarchitecture with a prominent apical dendrite and a very long axon, UMNs require a stable cell membrane, a lipid bilayer. Lipids can act as building blocks for many biomolecules, and they also contribute to the production of energy. Therefore, UMNs require sustained control over the production, utilization and homeostasis of lipids. Perturbations of lipid homeostasis lead to UMN vulnerability and progressive degeneration in diseases such as hereditary spastic paraplegia (HSP) and primary lateral sclerosis (PLS). Here, we discuss the importance of lipids, especially for UMNs.