Pharmacological modulation of septins restores calcium homeostasis and is neuroprotective in models of Alzheimer's disease.
Science
; 384(6699): eadd6260, 2024 May 31.
Article
in 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Calcium
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Amyloid beta-Peptides
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Tau Proteins
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Neuroprotective Agents
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Septins
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Alzheimer Disease
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Homeostasis
Limits:
Animals
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Humans
Language:
En
Journal:
Science
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: