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RNA splicing modulation of GluA1-flip isoform
- Molecular classification
- Ion channel, Receptor, AMPA receptor subunit, RNA splice variant
01
Overview
The GluA1-flip isoform is a splice variant of the GluA1 subunit of AMPA receptors, which mediate fast excitatory neurotransmission. The flip/flop alternative splicing event results in protein variants with distinct functional properties, affecting glutamate sensitivity, desensitization kinetics, and network excitability. Modulation of RNA splicing toward reducing GluA1-flip expression may offer a therapeutic approach for conditions like epilepsy.
- Other names
- GluA1-flipGRIA1-flipAMPA receptor GluA1-flip subunit
02
Mechanism of action
Modulation of GluA1 pre-mRNA splicing to alter the ratio of GluA1-flip to GluA1-flop isoforms, influencing AMPAR channel kinetics and neuronal excitability.
03
Biological functions
Synaptic transmissionExcitatory neurotransmissionSynaptic plasticityRegulation of neuronal excitability
04
Disease associations
EpilepsyNeurological disorders with hyperexcitabilitySeizures
05
Safety considerations
Potential for off-target splicing effectsLong-term effects of altered GluA1-flip expressionNeed for precise dose control to avoid excessive reduction of GluA1-flip function
06
Interacting drugs
Splice modulating oligonucleotides (SMOs)
1 more in the full profile.
07
Biomarkers
Ratio of GluA1-flip/GluA1-flop mRNA or protein levelsAMPA receptor-mediated excitatory postsynaptic currents (EPSCs)
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