Antagonist of neuronal store-operated calcium entry exerts beneficial effects in neurons expressing PSEN1ΔE9 mutant linked to familial Alzheimer disease.
Neuroscience
; 410: 118-127, 2019 07 01.
Article
en En
| MEDLINE
| ID: mdl-31055008
ABSTRACT
Alzheimer's disease (AD) is the neurodegenerative disorder with no cure. Recent studies suggest that dysregulated postsynaptic store-operated calcium entry (nSOCE) may underlie mushroom spine loss that is related to AD pathology. In the present study we observed that PSEN1ΔE9 familial AD (FAD) mutation causes mushroom spine loss in hippocampal neuronal cultures. We also demonstrated that amplitude of TRPC6-mediated nSOCE is increased in PSEN1ΔE9-expressing neurons and we suggested that inhibition of nSOCE may help to rescue synaptic defects in this model. We further established that nSOCE antagonist EVP4593 decreases PSEN1ΔE9-mediated nSOCE upregulation and rescues mushroom spines in PSEN1ΔE9-expressing neurons. Obtained results further highlight the connection between dysregulation of endoplasmic reticulum calcium signaling and synaptic loss in AD and suggest that calcium signaling modulators may have a therapeutic value for treatment of memory loss in AD.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Éteres Fenílicos
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Quinazolinas
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Proteínas de Unión al Calcio
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Presenilina-1
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Enfermedad de Alzheimer
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Proteínas de la Membrana
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Neuronas
Límite:
Animals
Idioma:
En
Revista:
Neuroscience
Año:
2019
Tipo del documento:
Article
País de afiliación:
Rusia