Analysis of NMDAR-Kidins220-ARMS Signaling Pathway in Stroke

Kinase D-interacting substrate of 220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning (ARMS), is a conserved membrane protein mainly expressed in brain and neuroendocrine cells, which is a downstream target of the signaling cascades initiated by neurotrophins and ephrins. Kidins220/ARMS is a component of the NMDAR complex that controls ERK and BDNF activation, which is critical for maintaining neuronal viability. Studies have shown that excitotoxicity caused by NMDAR overstimulation can significantly reduce Kidins220/ARMS levels in a model of cerebral ischemia stroke. Furthermore, Kidins220/ARMS knockdown reduced ERK activation and basal neuronal viability and increased neuronal death under excitotoxic conditions.

Fig. 1. Model of Kidins220/ARMS downregulation during excitotoxicity and ischemia. (López-Menéndez et al., 2009)

Our Services

At Ace Therapeutics, we use a multifaceted approach to analyze the molecular mechanisms underlying the regulation and downstream signaling of the NMDAR-Kidins220-ARMS signaling pathway in stroke. Using in vitro and animal models of ischemia stroke, we aim to elucidate the association of Kidins220/ARMS with NR2A and NR2B, and develop neuroprotective therapies on Kidins220/ARMS.

Our approach encompasses a variety of techniques, allow us to assess protein expression levels and elucidate the functional consequences of NMDAR-Kidins220-ARMS dysregulation. We focus on the following Kidins220/ARMS-related targets, and the specific experimental design can be customized according to client's needs.

• NMDAR- NR2A/NR2B
• Neurotrophin and ephrin receptors: tropomyosin-related kinase (Trk) and Eph
• Kidins
• ERK
• BDNF
• MAPK
• Janus kinase (Jak)
• Transcription activator
• NF-κB pathway

Workflow of NMDAR-Kidins220-ARMS Signaling Pathway Analysis

• We engage in active discussions with you to craft experiments to address specific research questions related to the NMDAR-Kidins220-ARMS signaling pathway in stroke.
• We perform a range of molecular and cellular analyses, including quantifying the levels of Kidins220/ARMS-related proteins, visualizing the subcellular localization of key signaling components.
• We use a high-throughput genomics approach to identify changes in gene expression patterns associated with the Kidins220-ARMS signaling pathway in stroke. These omics data are integrated and analyzed by bioinformatics tools to identify novel regulatory networks and signaling pathways.
• We combine the results of molecular and cellular analyses with high-throughput omics data to identify signaling cascades and potential therapeutic targets for Kidins220-ARMS.

With our expertise, state-of-the-art facilities, and collaborative approach, Ace Therapeutics is committed to helping clients discover and validate effective targets to target neuro-excitotoxicity in stroke. If you are interested in our services, please do not hesitate to contact us!

1. López-Menéndez C, et al. Kidins220/ARMS downregulation by excitotoxic activation of NMDARs reveals its involvement in neuronal survival and death pathways. J Cell Sci. 2009 Oct 1;122(Pt 19):3554-65.