Motor Neuron Diseases: Molecular Mechanism, Pathophysiology, and Treatments

The term “motor neuron disease” refers to a variety of devastating neurological disorders characterized by a generalized degeneration of motoneurons. The common clinical manifestations of such disorders are progressive muscle weakness and often death by respiratory failure. Inherited and sporadic forms occur. Further clinical distinctions are made according to the onset of the disorder and whether the disease involves only spinal and bulbar motor neurons (spinal muscular atrophy), or both the lower and upper motor neurons. The most common forms of motor neuron disease are spinal muscular atrophy with an incidence of 1:6000 to 10 000 newborns, and sporadic amyotrophic lateral sclerosis with a prevalence of 1:100 000, which corresponds to an incidence of 1:10 000. About 90% of all cases of amyotrophic lateral sclerosis are sporadic. This disorder affects mostly adults, has a typical clinical appearance, is noninherited, still incurable, and invariably fatal. Recent years have seen the identification of a variety of disease mechanisms, which all lead to the degeneration of motor neurons. Thus, pharmacological approaches that can interfere with degeneration and cell death can now be developed but are complicated by the fact that such therapeutic strategies might work only in subpopulations and not in all patients with this disease. Keywords: Amyotrophic Lateral Sclerosis (ALS); Motor Neuron Disease (MND); Neurotrophic Factors; Spinal Muscular Atrophy (SMA)