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].