肌萎缩性侧索硬化症和兴奋性氨基酸

Amyotropic Lateral Sclerosis and Excitatory Amino Acid

以α-氨基-3-羟基-4异恶唑-丙酸(AMPA)受体介导的Ca^(2+)通透性增加,Ca^(2+)流入比例增大而导致神经细胞死亡的理论已经明确。AMPA受体的谷氨酸受体2(GluR2)亚基的Q/R部位编辑率低下是散发性肌萎缩性侧索硬化(ALS)运动神经元死亡的主要原因。变异的铜-锌超氧化物歧化酶(SOD1)相关的家族性ALS(ALS1)是以AMPA受体含GluR2亚基的比例减少为基础;以延髓脊髓性肌萎缩症(SMBA)为代表运动神经元的死亡,不是AMPA受体所介导。ALS GluR2 Q/R部位核糖核酸(RNA)编辑的恢复可以考虑成为ALS治疗的特异方法,而AMPA受体拮抗剂可以防止ALS1运动神经元的变性。

α-amino-3-hydroxy-5-methl-4-isoxazolepropionic acid(AMPA) receptor,one of ionotropic glutamate receptors,has been proposed to play a critical role to initiate the neuronal death cascade in motor neuron disease by an increase of Ca^(2+) influx.These are at least two mechanisms to increase Ca^(2+) influx through Ca^(2+)-permiable AMPA receptor:a decrease of RNA editing efficiency at the GluR2 Q/R site and a decrease of GluR2 level relative to AMPA receptor submits.Deficient RNA editing of the AMPA receptor su...