Analysis of AMPA Receptor-mediated Excitotoxicity in Stroke

In neurons, mature α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are tetramers consisting of various combinations of GluR1 to GluR4 subunits. Hyperactivation of the AMPAR allows the influx of sodium ions into the post-synaptic neuron, which is associated with ischemic stroke-related excitatory neuronal death. However, the specific molecular mechanisms by which AMPAR, especially GluR2-containing AMPAR, induces neuronal death remain poorly understood. Although GluR2-containing AMPARs are calcium-impermeable, selective reduction of GluR2 expression, leading to an increase in Ca²⁺-permeable AMPA receptors, has been associated with an increased vulnerability of neurons to ischemic injury.

Fig. 1. AMPAR trafficking regulated by PKC. (Guo et al., 2021)

Our Services

At Ace Therapeutics, we specialize in a comprehensive molecular mechanistic analysis of AMPAR-mediated excitotoxicity in stroke. By elucidating the complex pathways involved, we aim to help our clients understand stroke pathogenesis and identify potential therapeutic targets. Our team of experienced and highly skilled scientists is committed to delivering accurate and reliable results.

We can identify and characterize these AMPAR-related protein-protein interactions, including:

• GRIP (glutamate receptor interacting protein)
• ABP (AMPAR-binding protein)
• SAP97 (synapse-associated protein-97)
• PICK1 (protein interacting with C kinase-1)
• NSF (N-ethylmaleimide-sensitive factor)
• AP2 (adapter protein 2)
• GAPDH

Our Approaches

• We employ a series of protein-protein interaction assays, including coimmunoprecipitation, colocalization studies, and surface plasmon resonance, to identify and characterize the interactions involved in AMPAR-mediated excitotoxicity.
• We offer live cell imaging techniques, such as confocal microscopy and two-photon microscopy, that enable real-time visualization of the dynamic processes of AMPAR internalization, calcium influx, and neuronal death.
• We offer techniques such as whole-cell patch clamp to assess the functional properties of AMPARs in in vitro models of stroke.
• We employ various molecular biology techniques, such as quantitative PCR, western blotting, and immunohistochemistry, to examine the expression levels, subunit composition, and localization of AMPARs in animal models of stroke.

Ace Therapeutics provides comprehensive molecular mechanism analysis services to elucidate the role of AMPAR-mediated excitotoxicity in stroke pathogenesis. We are committed to helping our clients develop drugs and peptides that selectively target AMPAR-related protein-protein interactions, providing new avenues for the treatment of stroke. If you are interested in our services, please do not hesitate to contact us!

1. Guo, C., & Ma, Y. Y. (2021). Calcium permeable-AMPA receptors and excitotoxicity in neurological disorders. Frontiers in neural circuits, 15, 711564.