Neurodazine functions as a neurogenic inducer, capable of promoting neurogenesis in pluripotent stem cells[1]. Neurodazine facilitates neurogenesis by activating the Wnt and Shh signaling pathways, while selectively inhibiting astrocyte differentiation in P19 cells[2].
In vitro, treatment of human SH-SY5Y neuroblastoma cells and murine Neuro-2a neuroblastoma cells with Neurodazine (2.5-5μM) for 10 days, Neurodazine significantly induced neuronal differentiation. This effect, mediated through the activation of Wnt and Shh signaling pathways, upregulated the expression of neuron-specific markers (Tuj1, MAP2, NF200, NSE) and promoted the expression of glutamate receptor subtypes (NMDAR1, GluK4, mGluR6)[3]. Co-treatment of human fibroblasts (hNF) with Neurodazine (2.5–4μM) and the hedgehog pathway inhibitor HPI-1 for 10 days, Neurodazine induced the transdifferentiation of fibroblasts into dopaminergic neuron-like cells, upregulated tyrosine hydroxylase (TH) and dopamine secretion, activated the autophagy pathway (increased expression of LC3, ATG5, ATG12), and inhibited apoptosis-related gene expression[4].
In vivo, intraplantar injection of Neurodazine (5μg) combined with complete Freund's adjuvant (CFA) in C57BL/6J mice during the juvenile stage (P21-P29), Neurodazine significantly enhanced resilience to anxiety-like behaviors induced by subthreshold acute restraint stress in adulthood (P90) and reduced serum corticosterone levels. Neurodazine also markedly ameliorated neurogenesis deficits in the hippocampal ventral dentate gyrus (vDG)[5].
References:
[1] Pérez-Caaveiro C, Pérez Sestelo J, Martínez MM, et al. Triorganoindium reagents in selective palladium-catalyzed cross-coupling with iodoimidazoles: synthesis of neurodazine. J Org Chem. 2014 Oct 17;79(20):9586-93.
[2] Kim GH, Halder D, Park J, et al. Imidazole-based small molecules that promote neurogenesis in pluripotent cells. Angew Chem Int Ed Engl. 2014 Aug 25;53(35):9271-4.
[3] Sorraksa N, Kaokaen P, Kunhorm P, et al. Rapid induction of dopaminergic neuron-like cells from human fibroblasts by autophagy activation with only 2-small molecules. 3 Biotech. 2024 Apr;14(4):115.
[4] Halder D, Kim GH, Shin I. Synthetic small molecules that induce neuronal differentiation in neuroblastoma and fibroblast cells. Mol Biosyst. 2015 Oct;11(10):2727-37.
[5] Yang C, Hu B, Gao Y, et al. Pain experience in juveniles promotes vulnerability to anxiety-like behaviors in adult mice by suppressing hippocampal neurogenesis. Biochem Biophys Res Commun. 2025 Aug 15;775:152170.
Neurodazine作为一种神经源性诱导剂，能够促进多能干细胞的神经发生[1]。Neurodazine通过激活Wnt和Shh信号通路以促进神经发生，并选择性抑制P19细胞的星形胶质细胞分化[2]。
在体外，Neurodazine（2.5-5μM）处理人源SH-SY5Y神经母细胞瘤细胞和鼠源Neuro-2a神经母细胞瘤细胞10天，Neurodazine通过激活Wnt和Shh信号通路，显著诱导神经元分化，上调神经元特异性标志物（Tuj1、MAP2、NF200、NSE）的表达，并促进谷氨酸受体亚型（NMDAR1、GluK4、mGluR6）的表达[3]。Neurodazine（2.5–4μM）与hedgehog通路抑制剂HPI-1联合处理人源成纤维细胞（hNF）10天，Neurodazine与HPI-1协同诱导成纤维细胞向多巴胺能神经元样细胞转分化，上调酪氨酸羟化酶（TH）和多巴胺分泌，并激活自噬通路（LC3、ATG5、ATG12表达上调），抑制凋亡相关基因表达[4]。
在体内，在C57BL/6J小鼠幼年期（P21-P29），Neurodazine（5μg）联合完全弗氏佐剂（CFA）腹腔注射处小鼠，Neurodazine显著增强了小鼠在成年期（P90）对亚阈值急性束缚应激诱导的焦虑样行为的抵抗力，降低血清皮质酮水平。Neurodazine显著改善了海马腹侧齿状回（vDG）的神经发生缺陷[5]。