EAAT2targeted

EAAT2-targeted refers to research and therapeutic approaches aimed at modulating EAAT2, the excitatory amino acid transporter 2. EAAT2 is the primary high-affinity glutamate transporter in the central nervous system, largely expressed by astrocytes and encoded by the SLC1A2 gene. By clearing extracellular glutamate, EAAT2 helps maintain synaptic and extrasynaptic glutamate homeostasis and protects neurons from excitotoxic injury. Impaired EAAT2 function or reduced expression has been associated with several neurological conditions, making it a focus for intervention.

Strategies in EAAT2-targeted research include upregulation of EAAT2 expression, enhancement of transporter trafficking to the astrocyte plasma membrane, and direct pharmacological activation of transporter activity. One class of agents, beta-lactam antibiotics, has shown the ability to increase EAAT2 expression in preclinical models, but translating these findings to safe and effective human therapies has been challenging. Gene therapy approaches using viral vectors to overexpress EAAT2 in targeted brain regions have been investigated in animals and early-phase studies. Other avenues explore small molecules, chaperones, or RNA-based methods to boost SLC1A2 expression or improve transporter function.

Potential applications span conditions characterized by excitotoxicity, including amyotrophic lateral sclerosis, ischemic stroke, epilepsy, Huntington’s disease, and Alzheimer’s disease. Challenges remain, including achieving selective, region-specific upregulation, crossing the blood–brain barrier, ensuring long-term safety, and avoiding off-target effects. As of the mid-2020s, no EAAT2-targeted therapy has been approved, with most work still in preclinical or early clinical stages.