(S)-5-Nitrowillardiine, AMPA / kainate agonist

Supplementary info

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

Activity summary

The Glutamate Receptor 1 also known as GluR1 is a subtype of AMPA receptors and part of the broader family of ionotropic glutamate receptors. These receptors including GluA4 and GluK5 are involved in fast synaptic transmission in the central nervous system. AMPA/kainate receptors including the kainate subtype mediate excitatory synaptic transmission by binding glutamate which induces a conformational change in the receptor allowing ion flow across the cell membrane. The mass of GluR1 is approximately 99 kDa and it expresses predominantly in the brain especially in regions like the hippocampus and cortex which are vital for learning and memory.

Biological function summary

AMPA/kainate receptors such as GluA4 and GluK5 play an important role in synaptic plasticity a foundation for cognitive processes like learning and memory. The AMPA/kainate receptor is typically found as a tetramer comprising various subunit compositions that define its properties such as calcium permeability and conductance. These complexes can exist as either homomeric or heteromeric assemblies that enable them to respond differentially to synaptic activity fine-tuning neuronal communication.

Pathways

The involvement of the Glutamate Receptor 1 in neurotransmitter signaling pathways is well-established notably in the synaptic vesicle cycle and long-term potentiation (LTP). LTP is critical for the strengthening of synapses an important mechanism underlying learning and memory. The receptors interact closely with proteins such as NMDA receptors another class of ionotropic glutamate receptors which serve complementary roles in these pathways. This interaction allows them to govern synaptic strength efficiently by modulating calcium influx and synapse plasticity.

Associated diseases and disorders

Dysregulation of the AMPA/kainate receptors is implicated in various neurological conditions including Alzheimer's disease and epilepsy. Alzheimer's disease associates with abnormal synaptic function where GluR1 and related receptors like GluA4 are often found to be dysregulated affecting memory and cognitive function. In epilepsy aberrant excitatory signaling through these receptors can lead to excessive neuronal firing and seizure activity. The study of these receptors in connection with specific proteins such as synaptic scaffolding molecules offers insights into potential therapeutic targets for these disorders.