Dal Prà Ilaria, Chiarini Anna, Armato Ubaldo
Histology & Embryology Section, Department of Life & Reproduction Sciences, University of Verona Medical School, Verona, Venetia, I-37134, Italy.
Neural Regen Res. 2015 Feb;10(2):213-8. doi: 10.4103/1673-5374.152373.
Astrocytes' roles in late-onset Alzheimer's disease (LOAD) promotion are important, since they survive soluble or fibrillar amyloid-β peptides (Aβs) neurotoxic effects, undergo alterations of intracellular and intercellular Ca(2+) signaling and gliotransmitters release via the Aβ/α7-nAChR (α7-nicotinic acetylcholine receptor) signaling, and overproduce/oversecrete newly synthesized Aβ42 oligomers, NO, and VEGF-A via the Aβ/CaSR (calcium-sensing receptor) signaling. Recently, it was suggested that the NMDAR (N-methyl-D-aspartate receptor) inhibitor nitromemantine would block the synapse-destroying effects of Aβ/α7-nAChR signaling. Yet, this and the progressive extracellular accrual and spreading of Aβ42 oligomers would be stopped well upstream by NPS 2143, an allosteric CaSR antagonist (calcilytic).
星形胶质细胞在迟发性阿尔茨海默病（LOAD）进展中的作用很重要，因为它们能在可溶性或纤维状淀粉样β肽（Aβ）的神经毒性作用下存活，通过Aβ/α7-烟碱型乙酰胆碱受体（α7-nAChR）信号传导经历细胞内和细胞间Ca（2+）信号传导的改变以及神经递质释放，并且通过Aβ/钙敏感受体（CaSR）信号传导过量产生/分泌新合成的Aβ42寡聚体、一氧化氮（NO）和血管内皮生长因子A（VEGF-A）。最近，有人提出N-甲基-D-天冬氨酸受体（NMDAR）抑制剂硝基美金刚会阻断Aβ/α7-nAChR信号传导对突触的破坏作用。然而，Aβ42寡聚体在细胞外的逐渐积累和扩散，会在更早的阶段被变构CaSR拮抗剂（钙分解剂）NPS 2143阻止。
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