4.3 Article

A novel NMDA receptor test model based on hiPSC-derived neural cells

Journal

BIOLOGICAL CHEMISTRY
Volume 404, Issue 4, Pages 267-277

Publisher

WALTER DE GRUYTER GMBH
DOI: 10.1515/hsz-2022-0216

Keywords

GluN2B; glutamatergic neurons; human stem cells; neurology; NMDAR; pharmacology

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N-Methyl-D-aspartate receptors (NMDARs) are crucial for brain learning and information processing. Dysfunction of NMDARs can contribute to neurodegeneration and drug addiction. Developing selective NMDAR modulators is a promising approach for treating these diseases. We established a hiPSC-derived neural cell system to investigate the effects of NMDAR modulators and pharmaceuticals on human neurons.
N-Methyl-D-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.

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