Store-Operated Calcium Channel Complex in Postsynaptic Spines: A New Therapeutic Target for Alzheimer's Disease Treatment.
Hua ZhangSuya SunLili WuEkaterina PchitskayaOlga ZakharovaKlementina Fon TacerIlya BezprozvannyPublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2017)
Mushroom dendritic spine structures are essential for memory storage and the loss of mushroom spines may explain memory defects in Alzheimer's disease (AD). This study demonstrated that Transient Receptor Potential Canonical 6 (TRPC6) and Orai2 form stromal interaction molecule 2 (STIM2)-regulated neuronal-store-operated Ca2+ influx (nSOC) channel complex in hippocampal synapse and the resulting Ca2+ influx is critical for long-term maintenance of mushroom spines in hippocampal neurons. A novel nSOC-positive modulator, NSN21778 (NSN), rescues mushroom spine loss and synaptic plasticity impairment in AD mice models. The TRPC6/Orai2 nSOC channel complex is a new therapeutic target and NSN is a potential candidate molecule for therapeutic intervention in brain aging and AD.
Keyphrases
- cerebral ischemia
- cognitive decline
- working memory
- randomized controlled trial
- subarachnoid hemorrhage
- bone marrow
- blood brain barrier
- transcription factor
- brain injury
- human health
- resting state
- mouse model
- protein kinase
- white matter
- spinal cord injury
- adipose tissue
- mass spectrometry
- high fat diet induced
- insulin resistance
- smoking cessation
- temporal lobe epilepsy
- wild type