Multidisciplinary Interventions in Motor Neuron Disease

Table 2

Pathophysiological processes in MND.

Pathophysiologic process	Comments
Excitotoxicity	Excessive postsynaptic glutamate induced stimulation of glutamate receptors such as NMDA & AMPA → massive calcium influx → nitric acid formation and neuronal death [21, 116].
Oxidative stress	Fibroblast culture from MND patients shows increased sensitivity to oxidative damage. Accumulation of free oxygen species → cell death. SOD1 is an antioxidant enzyme [116].
Mitochondrial defect	Abnormalities of mitochondrial morphology and biochemistry have been reported in sporadic MND patients, in SOD1 transgenic mice, and in cellular models [117, 118].
Impaired axonal transport	The relatively long length of motor neuron depends on effective transport systems. Evidence of abnormalities in this transport system has been reported in transgenic mice [119–121].
Neurofilament aggregation	Abnormal accumulation of neurofilament commonly occurs in many neurodegenerative diseases including MND [122, 123].
Protein aggregation	Intracellular inclusions have been observed in MND. The evidence is still unclear if these proteins are toxic or beneficial to the cell [21, 22].
Inflammatory dysfunction	Evidence suggests the possibility of an inflammatory process [23].
Deficits in neurotrophic factors and dysfunction of signaling pathway	Deficits in levels of neurotrophic factors, e.g., IGF-1, have been reported in MND [124–126].
Apoptosis	The final process in MND leading to neuronal death is said to closely resemble apoptosis, and markers of apoptosis have been detected in the later stages of the disease and animal models [127–129].