Pharmacological modulation of septins restores calcium homeostasis and is neuroprotective in models of Alzheimer's disease.
Science
; 384(6699): eadd6260, 2024 May 31.
Article
em En
| MEDLINE
| ID: mdl-38815015
ABSTRACT
Abnormal calcium signaling is a central pathological component of Alzheimer's disease (AD). Here, we describe the identification of a class of compounds called ReS19-T, which are able to restore calcium homeostasis in cell-based models of tau pathology. Aberrant tau accumulation leads to uncontrolled activation of store-operated calcium channels (SOCCs) by remodeling septin filaments at the cell cortex. Binding of ReS19-T to septins restores filament assembly in the disease state and restrains calcium entry through SOCCs. In amyloid-ß and tau-driven mouse models of disease, ReS19-T agents restored synaptic plasticity, normalized brain network activity, and attenuated the development of both amyloid-ß and tau pathology. Our findings identify the septin cytoskeleton as a potential therapeutic target for the development of disease-modifying AD treatments.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cálcio
/
Peptídeos beta-Amiloides
/
Proteínas tau
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Fármacos Neuroprotetores
/
Septinas
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Doença de Alzheimer
/
Homeostase
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Bélgica