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

Abstract

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.

• Amyotrophic lateral sclerosis
• calcium overload
• NMDA receptor activation
• neurotransmitter profile
• ischaemia