Glutamate-induced excitotoxicity pathway

The **glutamate-induced excitotoxicity pathway** is not a single molecular target but rather a pathological process in which excessive extracellular glutamate leads to overactivation of ionotropic glutamate receptors—primarily NMDA and AMPA receptors—resulting in toxic calcium influx into neurons. This triggers downstream cascades involving activation of enzymes such as nitric oxide synthase, generation of reactive oxygen species (ROS), mitochondrial dysfunction, ATP depletion, and ultimately neuronal apoptosis or necrosis. The process is implicated in acute brain injuries like ischemic stroke as well as chronic neurodegenerative diseases such as Parkinson’s disease and multiple sclerosis. While the pathway itself is not a druggable target per se, its key molecular components—especially the NMDA and AMPA receptors—are considered therapeutic targets for neuroprotection. Drugs like memantine (an NMDA receptor antagonist) have been developed to mitigate this form of cell death by blocking excessive receptor activation. However, clinical translation has been challenging due to side effects and limited efficacy observed with broad inhibition of these receptors.

Other names

Glutamate excitotoxicityExcitotoxicity pathwayGlutamate-mediated excitotoxicity

Inhibition of NMDA or AMPA receptors to reduce calcium influx and neuronal death