Analysis of Ischemia-Triggered Glutamate Excitotoxicity

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Excitotoxicity mediated by excess glutamate release is an important mechanism leading to injury after ischemic stroke and is also a potential therapeutic target for ischemic stroke. The release of glutamate is followed by the activation of its postsynaptic receptors. These receptors are of two kinds: ionotropic (N-methyl-D-aspartate (NMDA) receptors, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and kainate receptors) or metabotropic (mGluRs).

Fig. 1. Excitotoxicity and signaling pathways involved in ischemic stroke. (Qin et al., 2022)

Our Services

At Ace Therapeutics, we specialize in providing comprehensive analysis services for ischemia-triggered glutamate excitotoxicity. With years of experience in the field of stroke, our team of experts uses cutting-edge technologies to analyze the role of glutamate excitotoxicity in stroke, and discover targets that intervene in the pathological mechanisms of glutamate excitotoxicity (mainly involving developable therapeutic targets in glutamate release, reuptake mechanisms, NMDAR and its downstream cellular signaling pathways). We aim to help clients developing potential neuroprotective drugs and therapeutic approaches for the treatment of ischemic stroke.

Glutamate Receptor Activation Studies

Glutamate activates two types of ionotropic glutamate receptors (iGluR): AMPAR and NMDA receptors. We offer a comprehensive service to analyze the neurotoxic cascade of NMDAR and AMPAR mediated neuronal death in stroke.

Ion Homeostatic Imbalance Studies

This disruption leads to excessive glutamate release. At Ace Therapeutics, we investigate the complex mechanisms of ionic imbalance in stroke through advanced techniques and methods, and develop strategies to stabilize ion pump function. The possible targets include:

• DR region of NKA
• Gene products of NCX: NCX1, NCX2 and NCX3

Ca²⁺ Endocytosis Studies

Intracellular Ca²⁺ levels rise rapidly during ischemia, activating various calcium-dependent enzymes and disrupting mitochondrial function, ultimately leading to neuronal apoptosis. Ace Therapeutics is committed to helping our clients study the mechanisms of Ca²⁺ endocytosis in stroke and discover targets to effectively mitigate Ca²⁺ overload.

Impaired Glutamate Release and Reuptake Studies

Energy expenditure during ischemia disrupts the delicate balance of glutamate metabolism, leading to uncontrolled extracellular glutamate concentrations and subsequent neuronal toxicity. At Ace Therapeutics, we use cutting-edge technology to dissect the complex pathways involved in glutamate release and reuptake. Through meticulous analysis of glutamate transporter protein dynamics and synaptic transmission, we strive to identify targets for therapeutic intervention, including:

• TREK-1
• P2X7 receptor
• Glutamate transporter proteins
• Glutamate/cystine transporter proteins
• VRAC
• EAAT

Why Choose Us

• Our team of experts has many years of experience in the field of neuroscience, integrating expertise in diverse fields such as molecular biology, neurophysiology, and pharmacology.
• Our laboratories are equipped with cutting-edge instrumentation and advanced imaging technologies that allow us to perform high-resolution analysis of neuronal function and dysfunction in ischemic stroke.
• We offer customized solutions based on the specific needs of our clients. Whether we are designing experimental protocols or analyzing data, we work closely with our partners to deliver the best possible results.

Through our comprehensive analytical services, multidisciplinary approach, and state-of-the-art facilities, we strive to be your trusted partner. Contact us to move your stroke program forward!

1. Qin, C., et al. (2022). Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions. Signal transduction and targeted therapy, 7(1), 215.