UCPH-101, Selective EAAT1 inhibitor

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

Glutamate Transporter 1 (EAAT1) also known as SLC1A3 is a high-affinity sodium-dependent transporter responsible for the reuptake of glutamate from the synaptic cleft into glial cells and neurons. EAAT1 has a molecular mass of approximately 62 kDa and it is expressed abundantly in the central nervous system particularly in astrocytes. This transporter helps maintain low extracellular levels of glutamate preventing excitotoxicity which is damage caused by excessive stimulation of neurons. EAAT1 features as a critical component in maintaining the balance of neurotransmitters.

Biological function summary

Glutamate Transporter 1 regulates synaptic transmission and plasticity by removing glutamate from the synaptic cleft. It is essential for preventing excitotoxicity and maintaining glutamate homeostasis within the brain. EAAT1 does not form part of a larger protein complex but works alongside other glutamate transporters like EAAT2 and EAAT3 to manage extracellular glutamate levels. Its function is important for normal neural communication affecting processes such as learning and memory.

Pathways

The balance of neurotransmitters particularly the glutamatergic pathway involves EAAT1. It facilitates the regulation of glutamate levels ensuring effective synaptic transmission and neuroplasticity. EAAT1 functions alongside proteins such as glutamine synthetase which converts glutamate to glutamine thereby maintaining the glutamate-glutamine cycle. The transporter also integrates with the calcium signaling pathway influencing intracellular calcium dynamics through its role in excitatory neurotransmission.

Dysfunction of Glutamate Transporter 1 associates with several neurological conditions including epilepsy and amyotrophic lateral sclerosis (ALS). EAAT1's inability to manage glutamate levels can lead to chronic excitotoxicity contributing to these disorders. In epilepsy abnormal glutamate reuptake can result in hyperexcitability of neurons. In ALS EAAT1's impaired function may contribute to motor neuron degeneration. The protein interacts with EAAT2 another glutamate transporter which compounds the effects on neurodegenerative and neurological disorders when not functioning correctly.