Related Experiment Video
Updated: Mar 11, 2026
04:48
A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
Published on: July 10, 2018
9.8K
Store-Operated Calcium Channel Complex in Postsynaptic Spines: A New Therapeutic Target for Alzheimer's Disease
Summary
Loss of mushroom spines contributes to memory loss in aging and Alzheimer's disease (AD). A novel compound, NSN21778 (NSN), targets the STIM2-regulated TRPC6/Orai2 channel to restore spine stability and improve memory in AD models.
Area of Science:
- Neuroscience
- Molecular Biology
- Calcium Signaling
Background:
- Mushroom dendritic spines are crucial for memory storage.
- Spine loss is linked to memory deficits in aging and Alzheimer's disease (AD).
- The STIM2-mediated neuronal-store-operated Ca2+ influx (nSOC) pathway stabilizes mushroom spines but is impaired in AD.
Purpose of the Study:
- To identify the specific nSOC channel complex in hippocampal mushroom spines.
- To investigate the therapeutic potential of modulating this pathway for AD treatment.
- To evaluate a novel nSOC positive modulator, NSN21778 (NSN).
Main Methods:
- Electrophysiology and calcium imaging in hippocampal neurons.
- Utilized presenilin and APP knock-in mouse models of AD.
- Administered NSN21778 and assessed structural and functional synaptic changes.
Main Results:
- Identified TRPC6 and Orai2 channels forming a STIM2-regulated nSOC complex in mushroom spines.
- Hyperforin (TRPC6 activator) and NSN stimulated nSOC activity and rescued spine loss in AD models.
- NSN treatment reversed long-term potentiation impairment in APP knock-in mice.
Conclusions:
- The STIM2-regulated TRPC6/Orai2 nSOC channel complex is a novel therapeutic target for memory loss in aging and AD.
- NSN21778 demonstrates potential as a therapeutic agent for brain aging and AD.
- Restoring nSOC function offers a promising strategy to combat cognitive decline.
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