Survey of ALS-associated factors potentially promoting Ca2+ overload of motor neurons.
The deleterious consequences of Ca(2+) 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 Ca(2+ )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 Ca(2+ )influx through glutamate AMPA-receptors and voltage-gated channels of L-, N-, and P-type. Additionally, brain ischaemia can contribute to Ca(2+ )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.
Ionov
Ilya D
ID
Centre of Theoretical Problems in Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia. canyon1@rol.ru
D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid / Q000473:pathology* / Q000503:physiopathology*; D001923:Brain Chemistry / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death; D002540:Cerebral Cortex / Q000503:physiopathology; D006801:Humans; D009046:Motor Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000134:cerebrospinal fluid; D017470:Receptors, Glutamate / Q000502:physiology
D018377:Neurotransmitter Agents; D017470:Receptors, Glutamate; D002118:Calcium