Axonal Degeneration, Impaired Axonal Transport, and Synaptic Dysfunction in Motor Neuron Disorder

Motor neuron diseases (MNDs) are progressive disorders of the neurological system that have a strong effect on upper and lower motor neuron systems. Genetic mutations that contribute to the occurrence of motor neuron diseases lead to loss of protein homeostasis, dysregulated RNA metabolism, dysfunctionality of mitochondria, and impaired vesicle transportation. All these factors contribute to the impairment of the shape of axons resulting in their retraction. Axonal transportation is widely associated with the trafficking of essential cargos, neurotransmitters from neurons to the body organs, and a responsive signal back from organs to the neurons. Dysregulation in this system leads to neurological consequences. Some common and fatal diseases that arise due to MNDs are amyotrophic lateral sclerosis (ALS), survival motor neuron (SMN), spinal muscular atrophy (SMA), and progressive muscle atrophy (PMA). These diseases reflect symptoms of muscle cramps, dysphagia, spasticity, muscle weakness, atrophy, disturbance of neuropsychiatric behavior, and loss of homeostasis. There is a strong correlation between MNDs and axonal transport impairment, as evidence suggests the defective anterograde and retrograde transport, malfunctioning is considered an initial step in the development of neurodegenerative disease as well. Some commonly affected genes, such as DCTN1 and K1F5A, show a loss of functionality, thereby altering the axonal interactions. This chapter highlights the relationship between MNDs and impaired axonal transportation and their associated disorders.