Isoform 6 of Glutamate receptor 1

Glutamate receptor 1 (GluR1, encoded by GRIA1) is an AMPA-type ionotropic glutamate receptor subunit that mediates fast excitatory synaptic transmission in the central nervous system (UniProt: P42261-6). This isoform is a 916-amino acid transmembrane protein critical for synaptic plasticity and learning-dependent processes through calcium-permeable ion channel activity.

GluR1 is predominantly expressed in excitatory glutamatergic neurons throughout the brain and is essential for synaptic strength modulation and long-term potentiation. Dysfunction of AMPA receptors has been implicated in various neurological conditions affecting cognition and motor control (UniProt: P42261-6).

In Alzheimer's Disease, GluR1 isoform 6 shows significant downregulation in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.50 across TMT-labeled subcellular fractions (Chaparral AD proteomics). This reduction in AMPA receptor levels may contribute to the synaptic dysfunction and excitotoxicity observed in AD pathology, potentially affecting glutamatergic signaling and cognitive decline.