Gosset AMPA receptor Overview
The AMPA receptor (AMPAR) is a key ionotropic glutamate receptor that mediates fast excitatory synaptic transmission in the central nervous system. It is a tetrameric assembly composed of four subunits (GluA1, GluA2, GluA3, GluA4) and various auxiliary subunits (like TARPs, CNIHs, CKAMP44, Shisa6, SynDIG1, SynDIG4, GSG1L) that influence its function, pharmacology, and localization. AMPAR activation allows cation influx, leading to depolarization and signal propagation. Beyond fast neurotransmission, AMPARs are critical for synaptic plasticity, learning, memory, and brain development. Dysregulation of AMPAR function is implicated in numerous neurological and psychiatric disorders, including epilepsy (targeted by antagonists like Perampanel, Talampanel, Decanoic acid), neurodegenerative diseases (Alzheimer's, Parkinson's, ALS), Autism Spectrum Disorder, drug addiction, and schizophrenia. Despite being an important target, therapeutic development faces challenges such as CNS-related side effects due to widespread receptor distribution. Advances in understanding AMPAR structure and interactions with auxiliary/postsynaptic proteins offer new therapeutic avenues. AMPAR remains an important yet relatively unexploited therapeutic target.
Mechanism of Action
Drugs targeting AMPARs act either as antagonists (blocking receptor activity) or positive modulators (enhancing receptor function). Antagonists like Perampanel, Talampanel, and Decanoic acid suppress receptor activity and are used as antiepileptic agents. AMPAkines are positive modulators intended to enhance AMPAR function, explored for cognitive deficits.
Biological Functions
Disease Associations
Safety Considerations
- CNS-related side effects
- Difficulty selectively targeting affected brain regions due to widespread distribution