Survey of ALS-associated factors potentially promoting Ca2+ overload of motor neurons

The deleterious consequences of Ca2+ overload are thought to be a probable cause of motoneuronal death in ALS, although the overloading mechanism is currently unclear. In this paper some ALS-linked factors are analysed with regard to their influence on Ca2+ influx into neurons. Intensive cortex activity can render motor neurons susceptible to stimulation of calcium-permeable glutamate NMDA-receptors; increase in CSF concentrations of glutamate, glycine, and norepinephrine supposedly can intensify these receptors' activity. Elevated CSF levels of GABA and reduced levels of serotonin can promote Ca2+ influx through glutamate AMPA-receptors and voltage-gated channels of L-, N-, and P-type. Additionally, brain ischaemia can contribute to Ca2+ overload of motor neurons. Thus, ALS is characterized by the unique combination of factors potentially able to promote the overload of motor neurons with calcium.