Analysis of NR2A-PI3K-Akt Signaling Pathway in Stroke

Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), a pro-survival pathway in various neuronal cells, plays a key role in cell growth and neuronal repair and can be activated by NMDAR. The PI3K/Akt cascade induces neuroprotection through various pathways, such as phosphorylated inactivation of GSK-3β and BAD, phosphorylation of the Forkhead box transcription factor (FOXO) family phosphorylation and inhibition of their death-induced gene expression. Therefore, promoting the NR2A-PI3K-Akt signaling pathway is an important way to treat excitotoxic injury after cerebral ischemia. The protective effects of the PI3K/Akt signaling pathway against ischemic stroke have now been reported in neurons during hypoxia in vitro and against ischemic neuronal death in vivo.

Fig. 1. The schematic diagram of neuroprotection of TCM herbs for stroke via the PI3K/AKT-mediated pathways and key downstream molecules. (Gu et al., 2022)

Our Services

Ace Therapeutics provides reliable analysis services to investigate the mechanism of NR2A-PI3K-Akt signaling pathway in in vitro models and animal models of stroke. We aim to help our clients develop neuroprotective substances targeting the NR2A-PI3K-Akt signaling pathway as promising drug candidates for the treatment of ischemic stroke.

We conduct functional studies using cell-based assays and animal models to analyze the effects of NR2A-PI3K-Akt signaling pathway regulation on cellular responses, neuronal survival, and other stroke outcomes. Using advanced molecular analysis, we examine the expression levels and post-translational modifications of key molecules within the NR2A-PI3K-Akt signaling pathway. We can analyze the phosphorylation and inactivation of various upstream and downstream targets associated with Akt, including but not limited to:

• NMDAR- NR2A
• Insulin receptor substrate 1 (IRS-1)
• Akt
• PI3K
• FOXO family and their death-inducing gene expression, such as FasL and Bim-1
• p53
• Glycogen synthase kinase 3 beta (GSK3β)
• Pro-apoptotic B-cell lymphoma 2 (Bcl2)-associated BAD
• c-Jun N-terminal kinase (JNK)/p38 activator ASK1
• mTOR
• Nuclear factor κ light chain enhancer (NF-κB) in activated B cells
• Nrf2
• NOS
• Cyclic AMP response element binding protein (CREB)

With our expertise, state-of-the-art facilities, and collaborative approach, Ace Therapeutics combines experimental data with bioinformatics tools for comprehensive pathway analysis to identify key targets associated within the NR2A-PI3K-Akt pathway and potential therapeutic agents. If you are interested in our services, please do not hesitate to contact us!

1. Gu C, et al. The PI3K/AKT pathway-the potential key mechanisms of traditional chinese medicine for stroke. Front Med (Lausanne). 2022 May 31; 9:900809.