The Upper Motor Neuron—Improved Knowledge from ALS and Related Clinical Disorders

Abstract

Upper motor neuron (UMN) is a term traditionally used for the corticospinal or pyramidal tract neuron synapsing with the lower motor neuron (LMN) in the anterior horns of the spinal cord. The upper motor neuron controls resting muscle tone and helps initiate voluntary movement of the musculoskeletal system by pathways which are not completely understood. Dysfunction of the upper motor neuron causes the classical clinical signs of spasticity, weakness, brisk tendon reflexes and extensor plantar response, which are associated with clinically well-recognised, inherited and acquired disorders of the nervous system. Understanding the pathophysiology of motor system dysfunction in neurological disease has helped promote a greater understanding of the motor system and its complex cortical connections. This review will focus on the pathophysiology underlying progressive dysfunction of the UMN in amyotrophic lateral sclerosis and three other related adult-onset, progressive neurological disorders with prominent UMN signs, namely, primary lateral sclerosis, hereditary spastic paraplegia and primary progressive multiple sclerosis, to help promote better understanding of the human motor system and, by extension, related cortical systems.

Therapeutic Treatment of Superoxide Dismutase 1 (G93A) Amyotrophic Lateral Sclerosis Model Mice with Medical Ozone Decelerates Trigeminal Motor Neuron Degeneration, Attenuates Microglial Proliferation, and Preserves Monocyte Levels in Mesenteric Lymph Nodes

“…Deciphering the nature of this phenomenon may unravel strategies that help protect all ALS-vulnerable motor neurons from extended degeneration, and ultimately preserve motor abilities for a longer time. Additional analysis of ozone effects on upper motor neuron pathology in the M1 cortical area is equally warranted because this compartment is also prone to degenerate, both in humans [ 36 ] and in animal models [ 37 ]. A select preservation of those neurons that are needed for mastication indicates a beneficial effect of medical ozone on food intake and, subsequently, energy homeostasis.…”

Neuronal Circuit Dysfunction in Amyotrophic Lateral Sclerosis

“…One of the defining features of ALS pathology is the degeneration of upper motor neurons (UMNs) in the motor cortex and corticospinal tract (CST). Although UMN degeneration and dysfunction in ALS patients is well documented [41], the reasons for this selective vulnerability and the role of the cerebral cortex in aetiology and disease progression are yet poorly understood.…”

A patient-derived amyotrophic lateral sclerosis blood-brain barrier cell model reveals focused ultrasound-mediated anti-TDP-43 antibody delivery

“…ALS pathophysiology is complex, with multiple pathways converging into upper and lower motor neuron degeneration (1). Correspondingly, extensive evidence suggests early pathological changes in the upper motor neurons in the motor cortex supporting the development of motor cortex-directed therapies (3)(4)(5)(6)(7)(8)(9). However, targeting cortical neurons provides challenges due to the presence of the blood-brain barrier (BBB), which markedly limits the penetration of ALS therapeutics into the central nervous system (CNS) (2,(10)(11)(12)(13)(14).…”