Molecular Motors in Myelination and Their Misregulation in Disease

Molecular motors are cellular components involved in the intracellular transport of organelles and materials to ensure cell homeostasis. This is particularly relevant in neurons, where the synaptic components synthesized in the soma need to travel over long distances to their destination. They can walk on microtubules (kinesins and dyneins) or actin filaments (myosins), the major components of cell cytoskeleton. While kinesins mostly perform the anterograde transport of intracellular components toward the plus ends of microtubules located distally in cell processes, cytoplasmic dyneins allow the retrograde flux of intracellular cargo toward the minus ends of microtubules located at the cell soma. Axon myelination represents a major aspect of neuronal maturation and is essential for neuronal function, as it speeds up the transmission of electrical signals. Increasing evidence supports a role for molecular motors in the homeostatic control of myelination. This role includes the trafficking of myelin components along the processes of myelinating cells and local regulation of pathways that ensure axon wrapping. Dysfunctional control of the intracellular transport machinery has therefore been linked to several brain pathologies, including demyelinating diseases. These disorders include a broad spectrum of conditions characterized by pathological demyelination of axons within the nervous system, ultimately leading to axonal degeneration and neuronal death, with multiple sclerosis representing the most prevalent and studied condition. This review highlights the involvement of molecular motors in the homeostatic control of myelination. It also discusses studies that have yielded insights into the dysfunctional activity of molecular motors in the pathophysiology of multiple sclerosis.