Disse Paul, Aymanns Isabel, Ritter Nadine, Peischard Stefan, Korn Lisanne, Wiendl Heinz, Pawlowski Matthias, Kovac Stjepana, Meuth Sven G, Budde Thomas, Strutz-Seebohm Nathalie, Wünsch Bernhard, Seebohm Guiscard
Institut für Genetik von Herzerkrankungen (IfGH), Zelluläre Elektrophysiologie, Universitätsklinikum Münster, D-48149 Münster, Germany.
Chembion, GRK 2515, Westfälische Wilhelms-Universität Münster, D-48149 Münster, Germany.
Biol Chem. 2023 Jan 12;404(4):267-277. doi: 10.1515/hsz-2022-0216. Print 2023 Mar 28.
-Methyl--aspartate receptors (NMDARs) are central for learning and information processing in the brain. Dysfunction of NMDARs can play a key role in the pathogenesis of neurodegeneration and drug addiction. The development of selective NMDAR modulators represents a promising strategy to target these diseases. Among such modulating compounds are ifenprodil and its 3-benzazepine derivatives. Classically, the effects of these NMDAR modulators have been tested by techniques like two-electrode voltage clamp (TEVC), patch clamp, or fluorescence-based assays. However, testing their functional effects in complex human systems requires more advanced approaches. Here, we established a human induced pluripotent stem cell-derived (hiPSC-derived) neural cell system and proved its eligibility as a test system for investigating NMDAR modulators and pharmaceutical effects on human neurons.
N-甲基-D-天冬氨酸受体(NMDARs)在大脑的学习和信息处理中起着核心作用。NMDARs功能障碍在神经退行性变和药物成瘾的发病机制中可能起关键作用。开发选择性NMDAR调节剂是针对这些疾病的一种有前景的策略。这类调节化合物包括艾芬地尔及其3-苯并氮杂䓬衍生物。传统上,这些NMDAR调节剂的作用已通过双电极电压钳(TEVC)、膜片钳或基于荧光的检测等技术进行测试。然而,在复杂的人体系统中测试它们的功能作用需要更先进的方法。在这里,我们建立了一种人诱导多能干细胞衍生(hiPSC衍生)的神经细胞系统,并证明了其作为研究NMDAR调节剂及其对人类神经元药物作用的测试系统的适用性。