Excitotoxicity from excessive glutamate signaling contributes to neuronal death in stroke, ALS, AD, and PD.
Excitotoxicity occurs when excessive glutamate overstimulates NMDA and AMPA receptors, leading to calcium overload and cell death.
- Highest vulnerability
- Specific AMPA receptor subunits
- Efficient glutamate transport loss
- Excessive cortical input
- NMDA receptor dysfunction
- Early loss in HD
- Synaptic plasticity hub
- Age-related vulnerability
- Early in AD
- High glutamate input
- Climbing fiber excess
- Degeneration in ataxias
- NMDA receptor hyperactivation
- AMPA/Kainate receptors
- mGluR group I
- EAAT2 (GLT-1) loss
- Reduced uptake
- Synaptic spillover
- Calcium overload
- Mitochondrial dysfunction
- Nitric oxide production
- Caspase activation
- Riluzole (release reduction)
- NMDA antagonists (limited efficacy)
- AMPA antagonists
- Ceftriaxone (EAAT2 upregulation)
- Gene therapy approaches
- Calcium channel blockers
- Mitochondrial protectors
- Caspase inhibitors
- Excitotoxicity in ALS (2022)
- Glutamate and neurodegeneration (2021)